When the wind blows

.. the cradle will rock. So the rhyme goes, reminding us that the elements are indiscriminate in their destructive actions. At the time of writing Tropical Cyclone Iggy lingers off our shore, still a little undecided on if and where to make landfall.

TC Iggy

The Australian Bureau of Meteorology website provides a useful introduction to cyclone climatology. The northwest WA coast is the most cyclone-affected coastline in Australia. The annual averages are:

• 5 tropical cyclones form off the northwest coast
• 2 cyclones come ashore
• 1 of these will be severe, most often in March or April

Making tracks

Cyclone tracks vary considerably, some making U-turns or even loops. However, BOM notes that there is a preferred route starting in a south westerly direction, then turning more southerly and eventually south easterly when they travel as far south as the Pilbara.

The link with melioidosis

The path cyclones follow has been a matter of interest to the Micrognome for some time because of the link between melioidosis and severe weather in northern Australia. His team noticed there was a correlation between the direction cyclones took in a given year and the number of cases of severe disease.

Cyclone dynamics

Cyclone physics is complex and reflected in the variability of their destructive effect, wind speed, rainfall and duration. In general, BOM notes four main stages in the life-cycle of a tropical cyclone: formative, immature, mature and decay. We noted that the years when more cases occurred were years in which cyclones made landfall over the Northern Territory then followed a south westerly track. Years with cyclones approaching exclusively from the West and making landfall over the Kimberley or Pilbara coast were not bad years for severe melioidosis.

The fluid dynamics of interaction between a cyclone and the land it passes over  are most definitely complex. An added level of complexity is the rainfall that occurs in the cyclone’s decay stage. This looks like it may explain some of the excess cases observed in the NT.

At least we can predict cyclones like TC Iggy are unlikely to cause extra cases of melioidosis, while the likes of TC Carlos (see moving image) are a different kettle of fish.

Melioidosis info sources

• melioidosis clinical guideline
• the treatment of melioidosis
• melioidosis, a disease of surprises

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 Lab Without Walls project is ready to move up a gear, now that we have successfully completed an overseas deployment in a needy part of our region.

The following posts will show you what progress we’ve made already. They may give you some idea how you could help.

• Introduction
• Lab Without Walls in East Timor
• Opening the box
• When do we return?
• Operating on a mine site
• Thinking more widely

Lab Without Walls must now look closely at where the priorities lie.

• Where do we need to concentrate our efforts?
• What diseases should we target?
• Which patient groups are most urgent?
• What outcomes will we use to measure success?
• How best can we keep operating costs down? 

These questions will inform the foundational stages of our organisation.

A few things are certain:

• Our principal aim will be to improve the level of support for front line clinicians making point-of-care decisions about potentially life-threatening infections. 
• We will function as a not-for-profit agency, supporting other agencies whose primary role is the provision of a clinical service.
• Much of what we do will be to act as pioneers, blazing a trail for others to follow.

This won’t always be easy, but people have said repeatedly that what we set out to do couldn’t be done. It might be true that it won’t be done if we stick with the time-honoured methods. But we have shown several times over that it can be done. New and emerging technology, a clear set of clinical lab objectives and good logistic support can deliver accurate data on specific infections in places where little or no clinical microbiology service previously existed. To coin a phrase: Yes, we can!

Clearly, the places where the greatest gains will be made are where the biggest burden of disease coincides with the most under-resourced health service. Sadly, not all of these places are in developing countries overseas. There is a pressing need to use the insights we’ve gained from overseas lab deployments to meet the diagnostic support needs of remote area medicine in rural and regional Australia. We previously demonstrated advanced health threat assessment capability on a mine site in tropical Australia. Is it too much of a stretch to imagine Lab Without Walls modules operating in health centres on industrial sites, remote clinics and regional hospital labs?

The centralised service operated from a small number of clinical labs in urban centres has its merits, but falls a long way short of the point-of-care testing front line clinical staff are looking for. Recent infectious disease tragedies in nearby regional centres are confronting for those who have the imagination to see how things could improve. Lab Without Walls wants to close the gap between where we are now to where we need to be in the early and accurate diagnosis of infection.

Blood culture bottle top

Here are the notes you were promised: BC Med 2010

Download (PDF, 760.47KB)

Remember AIDA? She’s made a few appearances lately, most under the guise of clinical tropical medicine. But the first outing for this useful acronym was in connection with a clinical teaching unit on the management of septicaemia. Those notes will be handy if you miss out on today’s lecture (15:00hr, FJC LT, QEIIMC).

Download (PDF, 760.47KB)

Once again melioidosis is in the news. Queensland Health’s Dr Jeff Hanna has highlighted the melioidosis hot spot recently identified in the vicinity of Townsville, and Darwin melioidosis export Prof Bart Currie fronts up on the ABC’s 7.30 Report tonight.

Changing climate conditions in the north, particularly in the northwest, are thought to be responsible for some of the apparent increase in cases that can be blamed on severe weather events. But occupational activities as diverse as expansion of farming, the mining industry and even the local film industry could all contribute to an increase in meaningful encounters with a contaminated environment, and therefore subsequent cases of infection.

For a recent on-line review on melioidosis, see Life in the Fast Lane.

An update on how to treat melioidosis has just been posted by one of the open-source, on-line journals. This article provides a handy summary of current treatment options in a Table, dividing treatment into three phases of infection: 0, 1 and 2.

Melioidosis is a complex bacterial infection, treatment of which combines the urgency of treating rapidly fatal Gram negative septicaemia with the need for eradication of long-term persistent disease in pulmonary, soft tissue, skeletal and other organ systems. Incremental improvements in treatment have been made as a result of multicentre collaboration across the main endemic region of Southeast Asia and northern Australia.

There is an emerging consensus on the three main patterns of antimicrobial chemotherapy; initial (Phase 1) treatment, subsequent eradication (Phase 2) therapy and most recently post-exposure (Phase 0) prophylaxis. The combination of agents used, duration of therapy and need for adjunct modalities depends on the type, severity and antimicrobial susceptibility of infection. New antibiotic and adjunct therapies are at an investigational stage but on currently available data are unlikely to make a significant impact on this potentially fatal infection.

This treatment guide has been added to our FAQ page. The entire article can be obtained via the journal’s website.

More information on melioidosis

Reference:

Inglis, T.J. The Treatment of Melioidosis. Pharmaceuticals 2010, 3, 1296-1303 [Reference]

Why make a drama out of a crisis when you can turn in into a proper opera? The particular crisis the μGnome is concerned about here is the one that sucked him into μGnostics in the early days; the one that travels under a series of guises and that is variously known as septicaemia, systemic infection, blood poisoning, bacteremia and (for the four letter acronym fanatics) SIRS.

Before the days of high-tech medicine, the doctor had to hitch up his waistcoat as he bent over the patient to feel their sweaty brow and feel their thready pulse. There was weighty certainty in his prognostications as he proclaimed an imminent fever crisis. He might not have been able to tell you what the microbial cause of the infection was (μGnosis, or ætiology) but, by golly, he could make it all sound very grim.

The difference now is that we are no longer willing to wait for diagnostic certainty if it is at the price of increasing mobidity or risk of death. Septicaemia remains a potentially fatal condition, even in the best equipped centres. The diversity of potential infective agents will keep the attending physician guessing until we have faster, more accurate decision support tools. And a series of non-infective conditions may be mistaken for sepsis.

Which brings us to critical decision points: in a previous study we discovered almost by accident that if you performed a blood culture on the day the patient arrived in hospital there was a significantly lower mortality rate than if you delayed blood culture until the next day. We interpreted this incidental observation to mean that thinking about septicaemia early in the piece probably means you do something about it like start IV antibiotics earlier. In other words, it implies that there is a critical decision point somewhere in that first few hours after hospital admission. The clever people who are working up molecular tests to tell us exactly what the μGnosis is shortly after the patient arrives with a fever aim to exploit that crisis point. None of those new methods have quite made it over the line yet, so we have to make do with the good old blood culture for the time being.

Hence the opera, and not just any opera. The one that matters is AIDA. In this case the letters are an aide memoire for

• Assess (the patient)
• Inoculate (the blood culture)
• Decide (how to manage the patient), and
• Act (to start antibiotic therapy)

Specific skills need to be mastered in the correct use of blood cultures as part of the clinical investigative repertoire. These are summarised below in a Medical Interns talk. The part that the μGnome regrets cannot be provided on-line is the practical task of performing a blood culture. That is something practitioners will have to practice themselves. Happy bug hunting.

Download (PDF, 1.85MB)

Etiology of illness in patients with severe sepsis admitted to the hospital from the Emergency Department. Heffner AC, Horton JM, Marchick MR, Jones AE. Clinical Infectious Diseases 2010; 50: 814-820.

Heffner and colleagues took a look at how the ‘sepsis detectives’ perform in the challenging setting of a busy Emergency Department.

“Clinicians understand that sepsis is often a challenging diagnosis to establish at the bedside. Our report provides data supporting this assertion -namely, that in clinical practice ˜1 in 5 patients with suspected sepsis at admission may actually have a noninfectious disease that mimics the presentation of sepsis.”

This observational study of 211 patients admitted to an Emergency Department for severe sepsis, included 95 (45%) with positive blood cultures. Those with positive cultures were more likely to have vascular lines, and to have been in residential nursing homes. They also had a shorter time to antibiotic therapy in the ED. 44% patients with negative cultures had a clinical infection and 32% has a non-infectious disease that mimicked infection.

When the μGnome’s colleagues chewed the cud over this paper they highlighted a series of points:

• “sepsis” was categorised according to predefined criteria
• the study was in a single hospital centre between 2005 and 2007
• surgical patients were excluded from the study
• the focus was on very sick patients, possibly reflected in the relatively high mortality rate
• the timing of blood culture in relation to ED admission was unclear
• blood culture inoculation volumes and preliminary result turnaround was not reported

The μGnome agrees with the study’s authors. Working out who has an infective cause of severe sepsis syndrome is difficult in the ED.

• While early clinical intervention offers the best chance of preventing further deterioration, it is more difficult to identify a specific disease process.
• It is even more difficult to identify the causal infective agent with any degree of certainty.
• Pressure on ED staff to move patients on before an arbitrary deadline places the front-line clinician in an invidious position. A
• follow-up, prospective study including rapid molecular methods would be interesting.

One of the recurring problems in this area of clinical practice is the circular arguments that stem from the lack of a true reference standard for systemic infection. Blood culture is not, despite assertions in its favour, a ‘gold standard’:

• Many positive blood cultures from EDs contain possible skin bacteria that could easily have contaminated the culture during collection from a severely ill patient.
• False negative results may also occur as a result of prior antibiotic therapy, intermittent showering of bacteria into the peripheral circulation, or from inoculation of too small a quantity of blood.

These issues are likely to provoke further debate when we try to understand what a positive peripheral blood PCR assay means in the absence of a positive blood culture. The concept of a micrognosis was mentioned previously – this concept may help us find a way out of this circular diagnostic dilemma.