Followers of this blog will know how much a good cup of coffee matters to the MicroGnome. Regulars will know how to ask for their preferred cup in several languages. Australian coffee taxonomy is typically descriptive, direct and Anglo-Saxon; as you would expect from a nation with a high consumption: production index. Some will be surprised to know that Australia produces coffee. Not a lot, to be sure, but about as much as you’d expect from an island with relatively little suitable coffee-growing territory. However, that may have to change if we’re to keep up with our daily coffee needs.

• Coffee alert 1: scientists are beginning to warn that a series of coffee pests are already reducing output of the majority Arabica bean. Coffee borer and a fungal infection called coffee rust have reduced yields so much that well-known brands have had to put up their prices. The coffee berry borer, Hypothenemus hampei, is native to Africa. It is a small beetle recognised as the world’s most harmful coffee pest.  Interestingly, there is some evidence that commensal Wolbachia bacteria may help determine the sex of coffee borer beetles: proof that bacteriology is far from boring.
• Coffee alert 2: climate change monitors warn that even small changes in local temperature will significantly increase the reach of these threats to the global coffee crop, making coffee a sensitive indicator of global warming. We might whinge about the increasing price of a cappuccino, but spare a thought for the producers. Coffee is grown around the world in the tropical zone, where warmth, persistent moist air and good rainfall combine to support a viable crop. Coffee is therefore an important cash crop for many poorer parts of the world, and a loss of production translates directly to a loss of income for already disadvantaged communities.
• Coffee alert 3: If you take a look at the coffee growing map of the world, you can see considerable overlap with a range of tropical infectious diseases. Diseases such as tuberculosis, malaria, leishmaniasis, dengue and leprosy feature in many of the coffee growing areas. Neglected tropical diseases such as onchocerciasis, filariasis, other arbovirus infections, rickettsial diseases and nutritional disorders are also part of the epidemiological coffee-growing map. Then there are the food and water-borne diseases of these places: acute gastrointestinal infections, enteric fever, cholera and dysentery, giardiasis, amoebiasis, strongyloidiasis and other helminth infections.

Maybe we ought to look more closely at the links between growing coffee and tropical diseases. At very least, we ought to ask how the coffee industry could improve health benefits of the coffee producers. Something to consider the next time you enjoy your favourite wake-up drink.

MicroGnome, 2-JAN-12.

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.

5 key points on fever in international travellers (clinical problem)

• a travel history should be obtained from anyone with a febrile illness
• malaria should be excluded in anyone with a fever who has been in a malaria-endemic area recently
• then consider dengue & other arbovirus infections if there has been mosquito exposure
• do not forget the neglected bacterial tropical infections: enteric fever, leptospirosis, scrub typhus & melioidosis
• do not forget to ask about potential risk for sexually-transmitted infections & HIV/AIDS

Malaria: 5 point summary of highlights, further details in malaria module of Tropical Medicine teaching series

1. commonest fatal parasitic infection worldwide
2. prevented by avoiding bites from malaria-bearing Anopheles mosquitoes
3. all international travellers to malaria-endemic zone with fever on their return have malaria until proven otherwise
4. malaria cannot be completely ruled out by a single, one-off blood test
5. first line treatment recommended for uncomplicated malaria is based on an ACT-containing regimen unless good reason for choosing otherwise

Trop Med revision in a day? Who said it can’t be done.

Oxford Handbook of Tropical Medicine, 3rd edn

Here are some on-line resources to assist you:

1. Expedition medicine
2. Malaria
3. Fever in an international traveller
4. Arbovirus infections
5. Diarrhoeal disease
6. Enteric fever
7. Neglected bacterial diseases
8. Pneumonia
9. Snake bite
10. Envenomation
11. Leishmaniasis

Self assessment questions:

Clinical scenarios

Key information sources:

• WHO neglected tropical diseases
• CDC Yellow Book on travel health
• Oxford Handbook of Tropical Medicine
• Manson’s Tropical Diseases

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.

Our recently completed Lab Without Walls feasibility study in East  Timor was marked by a flurry of activity in the run-up to lab  deployment, and another burst of activity on our return. Our short stay  in Dili gave colleagues back home in Western Australia a welcome break  from our demanding schedule.

Here is our collection of material on the origin of the Lab Without Walls, its current  repertoire and future potential.

• Quick introduction
• Prehistory: Australian mine site, Central Sri Lanka
• Field Applications of Molecular Microbiology
• Lab Without Walls in East Timor
• What’s in the box?
• When’s the next gig?

All this talk of the Lab Without Walls, and we’ve said very little about what’s in the boxes we shipped. Now’s the time to open the lid and take a look inside. The concept is a portable molecular microbiology lab. That has been achieved in a series of modules, each of which can be quickly packed away in sturdy air freight boxes:

Sample prep module

1    Sample preparation module, comprising vortex mixer, bench top microfuge, heating block, automatic pipettes and an automated magnetic bead DNA extraction system (MagMax-24, Applied Biosystems)

Hospital (real time) thermocycler

2    Hospital real time thermocycler (StepOne, Applied Biosystems)

Mobile thermocycler & bioanalyzer

3    Mobile conventional thermocycler (Kyratech) and Bioanalyzer (Agilent Industries)

That is, of course, in addition to lab consumables and molecular reagents. The same combination of portable lab equipment can be used to deliver a wide range of pathology tests including:

• Mycobacterium tuberculosis in respiratory samples from patients with suspected tuberculosis
• MANTRA genotyping of M. tuberculosis
• Other Mycobacteria from patients with HIV/AIDS
• Plasmodium parasites in blood from patients with suspected malaria
• The top 12 bacteria found in blood cultures from septicaemic patients
• Bacteria responsible for pelvic inflammatory disease
• Dengue, Japanese encephalitis and other arboviruses in blood
• Quality control and troubleshooting assays
• Leptospira, Orienta and other bacteria in blood from febrile patients.

Want a quick tour with the Lab Without Walls team?

Here is what we can do, based on our recent feasibility study in Timor Leste.

The questions about when and how we return to continue our infectious disease field work in East Timor started on our last day in the Bairo Pité Clinic. Previous field lab visits to central Sri Lanka and northern Malaysia had prepared us for the stress of separation. Managing expectations comes with the territory.

We aim to develop, deploy and demonstrate capability, but our small team does not yet have the capacity to continue a prolonged campaign on our own. What we did last week in Dili was more like a preliminary reconnaissance; a feasibility study for future in-country development activity.

This first formal project by Lab Without Walls looks a bit like a road show, with its supporting cast of logistic and technical experts. Experience has shown that it is these support activities that make or break a field lab deployment. Interesting then that inspiration should come from the entertainment industry via the inner pages of the West Australian weekend paper. The up-coming U2 gig will feature a huge 360º stage known as ‘the Claw’ for the band that takes 4 days to assemble and two to pack up. We can do better than that with our malaria/TB/dengue/septicaemia/STD lab – one day to set up and run technical checks; a few hours to dismantle and pack away. And the mobile module can be set up to support a remote clinic in around 30 minutes. Just imagine what could be achieved with a logistic support team of 240 roadies in a country the size of East Timor. But this doesn’t quite answer the question.

We have demonstrated technical capability. The next stage of development is gathering financial, technical and ongoing technical support. If the dream of TB, malaria and HIV eradication is to be realised in a population around the size of the Perth metro area, we need to find Timorese staff to take the toolbox outside the capital, operate it to support community health programmes and develop an accurate appreciation of how to target scarce resources. This may all take a bit of time. The quicker we can raise the support, the sooner we will return.

So why all the emphasis on one of the back office functions of medical care? Well, if you think how much decision-making depends on pathology tests, try re-imagining your doctor working out what antibiotics to use, how long to use them for and how to cope with a serious outbreak in a country where no hospital currently cultures any clinical sample, where no antibiotic sensitivities are tested and where no definitive tests are available to check screening test performance. We might not be able to do it all on a shoestring budget, but there are new lab methods that would take the guesswork out of tackling headline infectious diseases like TB and malaria. Small lab footprint; modular concept; flexible test repertoire. The Lab Without Walls Team demonstrated that capability under austere conditions last week.

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

Now that the MicroGnome can reliably get lecture notes onto this Blog, here is the Malaria series for students of tropical medicine:

The ASM/ACTM Parasitology & Tropical Medicine Masterclass earlier this month was an excellent opportunity to catch up with leading experts in the field. The MicroGnome brings you a series of snapshots highlighting the weekend’s teaching. The edited highlights will be presented at the next QEIIMC Tropical Medicine Breakfast:

• Introduction to faecal parasite examination (Lynne Garcia)
• Blood parasites (Lynne Garcia)
• Molecular methods in parasitology (Jaco Verweij)
• Medical Entomology (Richard Russell)
• Clinical cases of parasitic infections (clinical centres around Australia)

Manson’s Tropical Diseases. 22nd edn. Ed GC Cook, AI Zumla. Elsevier, 2009. ISBN 978-1-4160-4470-0

When a medical textbook reaches its 22nd edition, it has clearly become an institution. Manson’s Tropical Diseases has become one of the leading sources of authoritative opinion on tropical medicine in the English-speaking world. The most recent edition goes well beyond the standard fare of tropical infectious diseases to cover the challenges of other medical specialties in the tropics and a collection of non-infective conditions. This diverse range of topics has been presented to a consistently high standard; a notable editorial achievement for a topic with such breadth. 89 chapters are divided into 12 sections and supplemented by on-line material in a series of 5 appendices. It adds up to 1783 pages of carefully crafted professional writing.

From recent use [FACTM on-line modules; Malaria & Arbovirus Infections] I have been particularly impressed by Nick White’s magisterial chapter on malaria and David Smith’s group’s review of arbovirus infections. Both chapters are examples of lucid prose that is a pleasure to read for reading’s sake. They are also one of reasons Manson’s Tropical Diseases has sustained its success over so many editions, through making the familiar read as new while making the genuinely novel accessible to a wider audience. The editors have achieved this difficult balancing act by retaining many of their chapter authors from the 21st edition.

Manson’s Tropical Diseases is recommended further reading for the FACTM pt 1 exam.

Sections: underlying factors in tropical medicine, symptoms and signs, system-oriented disease, related specialties in the tropics, environmental/genetic disorders, viral infection, rickettsial infections, bacterial infections, mycotic infections, protozoan infections, helminthic infections, ectoparasites.

Not only is today ANZAC Day; it’s also the day we note the achievements and continuing challenges of the Rollback Malaria campaign – World Malaria Day.

To mark the occasion, the Lancet has run a special feature edition on malaria.

The μGnome has nailed his colours to the mast in our FACTM pt 1 malaria series. Here is a short summary; highlights of the malaria unit.

Download (PPT, 910KB)

Oxford Handbook of Tropical Medicine. Eddlestone M et al. 3rd edn. Oxford University Press, 2008. ISBN 978-0-19-920409-0

42 contributors. 22 chapters. 843 pages

This small textbook has been recommended by the Australasian College of Tropical Medicine as an essential core text for those studying towards the Part 1 Fellowship exam. There is good reason for this recommendation. This small, easily portable volume provides a comprehensive and authoritative guide to this area of clinical medicine. Its contents go well beyond the inner circle of tropical infectious diseases, envenomations and nutritional disorders to include tropical paediatrics, mental health, multisystem diseases and covers topics relevant to other areas of general medicine, obstetrics and gynaecology.

Guidance is practical and details of drug administration and other key aspects of acute patient management are plentiful.

This is the third edition, and contains a series of updates to the previous editions including new material on non-infective conditions such as heat stroke and altitude sickness. There is quite a bit of integration through cross-referencing and supplementary coverage in other chapters. For instance, the well-crafted chapter on Malaria (Ch 2) might have the last word on the infection, but there is also a well-made reminder about malaria in the chapter on multi-system infections (Ch 18: p668). Indexes can serve this function if you have the time to be methodical, but any busy clinician will tell you that pressure of work will rarely allow you that luxury. Well thought out contents and information layout are at the heart of a useful clinical handbook. As always, the proof of the pudding is in the eating, and in this case the Oxford Handbook stays on my desk, close to the phone. It gets used most days; more often than the authoritative Manson’s Tropical Diseases.

But no textbook is perfect. If I were asked to make any recommendations for the fourth edition I’d bring the contents list forward. Page ix buries the all-important contents between acknowledgements and a list of colour plates. Unfortunately the grey page markers do not line up with the contents list on p ix or the back cover. But these are cosmetic criticisms. The heart of this book is made of gold.

Oxford Handbook of Tropical Medicine, 3rd edn

The second Charlie’s postgraduate Tropical Medicine sessions takes place next Tuesday (27th April)  at 06:50 in the ED seminar room. Notes can be found on this site here.

This is part of the FACTM pt 1 series, and concludes our malaria unit.

Revision of the earlier two modules is also available on this site.

A light breakfast will be provided.

For those who’ve been following the μGnome’s series on all things malarial, the full set of learning modules can now be found on the Priobe Net Plasmodium page, along with an interactive malaria risk map and other malaria resources.

Powerpoint files can be downloaded in PDF for personal and educational use. There are separate PDFs here if all you need is the Plasmodium life cycle or the mosquito recognition chart. A link has been added to the WHO interactive travel health map. This allows you to update the information as changing malaria risk alters the global risk map. If studying for the FACTM pt 1, note the chapters in the recommended list of short textbooks, and a superbly written chapter on malaria in Manson’s Tropical Diseases by Nick White.

Malaria modules 3 and 4

The μGnome has finished preparing Malaria module 3 and Malaria module 4. These cover public health, travel health and expedition medicine aspects of malaria and vector biology. The two mini-lectures are presented here to help those studying for the FACTM pt 1 exam later this year. They complement modules 1 and 2.

Download (PDF, 1.91MB)

Download (PDF, 358.12KB)

More details can be found on the excellent Malaria site run by the WHO.

Settings for which the μGnome needed professional travel health and expedition medicine advice included Brazil and Sri Lanka. Click on the links for more on those expeditions.

• Clinical Tropical Medicine sessions started yesterday at the QEII Medical Centre with malaria 1 and 2
• Self-assessment questions follow for those thinking about doing the FACTM part 1 exam this year
  • Here are some questions based on the first two Malaria modules.
  • Additional self-assessment exercises for prospective candidates on the ACTM website .

Problem 1

What parasitic infection is this and why?

(both results are from the same blood sample)

Show answer

Problem 2

What infection is this and why?

(both views are from the same blood film)

Show answer

Here’s the clinical parasitology mini-lecture you may have missed, now in its new, minimalist version.

Download (PDF, 778.59KB)