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 first thing you notice on your way into the Bairo Pité Clinic is a small collection of very grubby vehicles; some held together by stickers from sponsors and other aid organisations. Not a bit like the clean white UN Prados and Land Cruisers that line the streets of Dili, these vehicles take clinic staff and visiting volunteers to outreach clinics well beyond the city’s edge.

When your eyes adapt to the relative gloom under the awnings, you see a gaggle of prospective patients waiting their turn for an appointment with Dr Dan. Dan Murphy’s personality looms large in the Bairo Pité Clinic, an NGO that provides a large slice of the acute health care in Dili. An American physician, Dr Dan sees at least 250 patients per day and has dealt with over 500 at times of great need.  His tall stature, commanding presence and sharp clinical acumen attract a stream of visiting medical students and junior doctors who join his daily clinical rounds for a regular dose of teaching on the run.

It isn’t long before you start to hear the rattling, productive cough that afflicts many of the clinic’s patients. When asked what the commonest medical complain was, Dr Dan replied that it was without any doubt tuberculosis. You don’t need surveillance data to work out that TB is a huge problem here. But with only acid fast stains available and no concentration or culture methods, laboratory-confirmed aetiology of pneumonia is an unimaginable luxury.

Not just TB. So many of the other conditions seen are either primary infection or the consequences of infection. A snapshot from just a couple of days at the Bairo Pité Clinic included malaria, pelvic inflammatory disease, HIV/AIDS, infective endocarditis, post-rheumatic heart disease mitral stenosis, meningitis, soft tissue abscess and tropical ulcers. Tragically, many of these conditions were easily recognisable because they had been allowed to run their course by patients who lacked the means to do anything about it. Further compounding this sorry tale were the family groups represented by several members attending the same TB clinic.

I was there with a colleague from the Lab Without Walls Foundation, looking at the feasibility of establishing clinical laboratory support for detection of several tropical infectious diseases. We flew in with various bits of portable lab gear in a small collection of air freight boxes, hoping to show the potential for direct molecular analysis of clinical samples in a clinic without much pathology support.  We knew there was no culture, but did not know exactly what else had already been done.  One thing we were clear about was the need to hose down unrealistic expectations. We were very careful to explain that we were not there to make a diagnosis or to replace an existing conventional approach.

Our planned programme was simple but ambitious. In four days we would run a series of molecular tests at a rate of one type per day: septicaemia, tuberculosis, malaria and PID. We took additional back up for genetic fingerprinting of tuberculosis bacteria, and for identification of other mosquito and tick-borne diseases (dengue, Japanese encephalitis and scrub typhus). But someone mischievous had other plans. First of all, a public holiday was called for the first two working days of the visit, bringing about a modest change of plans and a change of location for our lab work. Secondly, the party mood spilled over to delay our start by a day, and lastly the return to work on our last working day was accompanied by a series of power cuts. Power outages caused run failures on each item of equipment we used, requiring repetition of tests, a great deal of ingenuity and a monumental dose of patience.

In spite of it all, and quite possibly because of it, we had good reason to join the party mood at the end of our working week. The reason we felt an urgent need to pop a bottle of champagne was successful demonstration of the bacteria that cause tuberculosis in clinical samples, starting from scratch. Every bit as exciting (for crazy bug hunters) was the detection of malaria by our in-house molecular method in samples that had been checked and declared negative by standard microscopic examination. Evidently, the molecular (PCR) method is more sensitive than blood film examination. What of the other tests? Time and power supply didn’t allow us to complete our preliminary work on these tests during the deployment. Development will have to continue back at the Western Australian home base. Those celebrations will have to wait until the next Lab Without Walls project deployment.

You have to wonder what health expectations the youngest generation of Timorese have. It is clear to anyone involved in international health development how much could be achieved with a small fraction of the resources at our disposal in Australia. There is another thought nibbling away at the back of the mind – with the right tools and the community support, it might just be possible to eradicate at least one of the headline infectious diseases within a generation. A worthy goal that could be brought a step closer by your support.

More detailed reports on how the work was done will follow: travel reading [FEVER, Sonia Shah, 2010].

MicroGnome’s correspondent in Dili, December 2010.

Lab Without Walls project 2010/Dili/01 is supported by

Beware!  We had little warning. The Stafinator is here; scourge of staphylococci, decoloniser par excellence. If it needs antibacterial armour, he’ll put the tanks on the streets. If you have an exotic microbe lurking under cover, he’ll be onto your case. And as for the Resistance, he’ll be only too HAPI to make life difficult for them.

Crazy bug hunters are skeptical.  Fascinellas are laying low. The μgnome is quaking in his boots.

The μgnome scurried out of his burrow yesterday to make a few points about applied cell biology for microbiologists. The main thrust of his argument was that as we have the technology at hand, the question is no longer ‘can we do it?’ It’s a matter of practical application – what can be done with the technology, what specific applications are chosen, when these should be used and what should be done with the results.

The μgnome suggested a short list of potential clinical microbiology applications:

• attribution of a causal role to a given priobe or causal agent
• prediction of the likely course of infection
• targeting of early antimicrobial interventions
• guidance on the efficacy of public health control measures

The μgnome highlighted the possible role for advanced microscopy tools with two cases of ophthalmic infections; one parasitic, the other fungal.

Key microscopic methods demonstrated were:

• confocal microscopy (Acanthamoeba, mycorrhizal fungi)
• high resolution scanning electron microscopy (black & white images with subtitles!)
• whole slide scanning

Other methods discussed were

• flow cytometer analysis of fluorescent live/dead labelled bacterial cells
• small animal imaging for fluorescent probes
• image based reporting for parasites, fungi and mycobacteria

Asked to predict where this was likely to make a difference in clinical practice, the μgnome predicted that it would be image-based reporting of early growth bacteria in blood cultures and other sterile fluids, and possibly targeted live/dead cell analysis of drug-bug combinations to provide an early guide to antibiotic efficacy.

μgnome, 26th March