Infectious diseases

To the Editor: The recent editorial by Collignon and colleagues challenged Australian physicians and health care leaders to confront the rising burden of methicillin-resistant Staphylococcus aureus (MRSA).1 Compared with Australia, the United States has a bigger problem with MRSA; more than 60% of all hospital-acquired S. aureus infections are now caused by MRSA.2 Appropriately, the medical community has made an urgent call for action. For example, the Institute for Healthcare Improvement (a not-for-profit organisation based in the US that aims to improve health care throughout the world) incorporated specific MRSA prevention measures into its recent 5 Million Lives Campaign (see http://www.ihi.org/ihi). One of these prevention measures, a recommendation for active surveillance, has generated controversy. Specifically, the cost-effectiveness of this strategy is still vigorously debated in the infection control literature.3 At present, it is unclear what surveillance testing method should be used in the laboratory, and whether testing should be done for all patients or just those identified as high risk. The cry for help from community activists in the US and the United Kingdom has reached the ears of their legislative representatives. In two northern US states, lawmakers are considering bills that require universal active surveillance in their hospitals. Mandating resource-stretched health systems to implement obligatory active screening is not a prudent use of resources. The Society for Healthcare Epidemiology of America and the US Association for Professionals in Infection Control and Epidemiology recently published a joint position paper opposing this legislative activity, noting that data in support of active surveillance have been restricted to high-risk populations.4 We support this position and remind readers that active surveillance does not obviate the need for adherence to basic and consistent hand-hygiene practices. Complacency and lack of clinical leadership remain the greatest challenges in the efforts to reduce the transmission of MRSA. Why do we accept this epidemic as a fact of life as our health care workers complacently contribute to the nosocomial transmission of MRSA? By implementing simple prevention policies, feedback of data on nosocomial transmission of MRSA, and increased infection-control education, we have achieved a 22% reduction in MRSA infections in our network of community hospitals.5 Still, we acknowledge the absence of a zero-tolerance approach to failures in hand-hygiene practices. More needs to be done. We challenge our clinical leaders to demand higher standards for hand hygiene. Most cases of nosocomial MRSA transmission represent failures of basic hygiene practices. The problem is surmountable. Infection control is not a skill of a few, but the responsibility of every team member. The onus is on all of us.

Luke F Chen · Deverick J Anderson · Keith S Kaye · Daniel J Sexton

In reply: We thank Woollard for his comments on hand hygiene. While important, hand hygiene is just one component of what is needed to decrease the spread of methicillin-resistant Staphylococcus aureus (MRSA) in hospitals. Decontamination of the environment, contact precautions for colonised patients, active surveillance and screening, effective programs to prevent common infections such as intravascular catheter sepsis, good antibiotic stewardship and better hospital design are also indispensable.1 We do not accept that “There have been no properly controlled trials, with clinically important endpoints, of currently recommended hand-hygiene practices”. For instance, the recent study quoted by Woollard showed that hand hygiene reduced infections hospital-wide, using the clinically important endpoint of serious bloodstream infections (MRSA and antibiotic-resistant gram-negative bacteria).2 Thus, at least two large peer-reviewed studies show that alcohol-based hand-hygiene programs reduce hospital-acquired MRSA infections2,3 (Level III evidence4). There is nothing wrong with using disposable gloves, as suggested by Woollard, provided they are changed every time a health care worker moves between patients. Otherwise, gloves spread MRSA just as efficiently as unclean hands. Applying good-quality hand-hygiene products is less cumbersome than changing gloves and also allows direct human contact, which Woollard reminds us is important to patients. How MRSA is spread in hospitals is now well known — our problem is getting health care workers to remember to practise good hand hygiene all the time, every day, before and after every patient contact. The data shown by Ferguson and Van Gessel reaffirm how common and serious a problem we have with MRSA bacteraemia. They estimate there are about five episodes per 100 000 people annually across Australia. However, we believe that the true rate is double this. The rate of S. aureus bacteraemia (ie, MRSA and methicillin-sensitive S. aureus combined) in Australia is around 35 per 100 000 per year,5 with 27% caused by MRSA.5 This crudely translates to an MRSA rate of 9.5 per 100 000. The rates are probably much higher in the states with more health care-acquired MRSA (New South Wales and Victoria). More recent data suggest that 36% of hospital-acquired invasive S. aureus infections were caused by MRSA, with the highest percentages in NSW (41%) and Victoria (39%).6 It is also worth noting that, when MRSA bacteraemia became notifiable in England in 2001, there was a 50% increase in reported S. aureus bacteraemia episodes.1 This suggests that under-reporting is common in any voluntary reporting scheme, and is also likely for Australian data. Worryingly, Chen and colleagues point out that MRSA is an even bigger problem in the United States than in Australia. However, we are not far behind.6 Although we share their concerns about legislative impositions, some external controls and measurements can be an advantage. Western Australia, the only Australian state where MRSA is notifiable, has the lowest rates of health care-associated MRSA. While we do not want imposed “one size fits all” legislated controls, we do need change: the practice of the past 40 years has not worked. Every institution needs to have an effective MRSA control program, with components chosen according to the local situation. Institutions should measure MRSA and report centrally, especially if their rates are high and not falling continually (eg, over a year). Shop-floor quality improvement programs with empowered workers are much better than top-down management-imposed regulation (eg, from government). We need to shake our complacency and that of our health care colleagues, accept clinical leadership and take control. Otherwise, legislative controls will be imposed on us.

Peter J Collignon · M Lindsay Grayson · Paul D R Johnson

The first IAS conference to highlight biomedical prevention was held in Sydney in July 2007 Over 5000 delegates from 133 countries met in Sydney in July for the 4th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention, the first major international conference on the biomedical aspects of AIDS to be held in Australia. It was also the first conference in this series to include prevention in its title and to assign a central role to prevention research in the scientific program, alongside basic science and clinical research. Coinciding with the conference was the release of the Sydney Declaration, which calls for 10% of all resources devoted to HIV programming to be dedicated to research1 (Box). The conference provided Australia with an opportunity to benefit from the presence of world-leading scientists from a number of disciplines, as well as to showcase outstanding Australian achievements in HIV research. Clinical research, treatment and careAccording to the World Health Organization, the number of people receiving antiretroviral therapy (ART) worldwide now exceeds two million, which represents 28% of the adults, but only 15% of the children, who urgently need treatment in low- and middle-income countries. Debrework Zewdie (Director, Global HIV/AIDS Program, World Bank, Washington, DC, USA) reported that, as ART rollout continues at a fast pace in developing countries, new challenges are being recognised, including the “brain drain” of health professionals, limited laboratory facilities to monitor treatment, lack of access to the more costly regimens that limit toxicity or act as second-line treatment regimens, the coincident epidemic of tuberculosis fuelled by both the HIV epidemic and increasing resistance to standard antituberculosis drugs, and the need to increase coverage to include the most vulnerable, including injecting drug users (conference abstract MOPL1, available online at the conference website2). The conference highlighted research on new agents and new ways of using existing drugs to improve clinical outcomes. New drugs included etravirine (active against HIV resistant to first-line non-nucleoside reverse transcriptase inhibitors) (abstracts WESS204-1 and WESS204-2), raltegravir (the first integrase inhibitor) (abstract TUAB104), and maraviroc (the first chemokine inhibitor) (abstract WESS104), all of which showed efficacy in Phase III clinical trials. Patients with multidrug-resistant HIV following treatment with existing drug classes can now expect, in well resourced countries, to achieve full viral suppression with the newer agents. Other ART agents in earlier phases of development include apricitabine (abstract WESS203), active against lamivudine-resistant HIV, and being developed by an Australian pharmaceutical company, and PRO 140, a CCR5 monoclonal antibody, which could potentially be administered subcutaneously once weekly (abstract WESS201). The long-standing debate about when to start ART was reignited during the conference. The Children with HIV Early Antiretroviral Therapy (CHER) study in South Africa enrolled 252 infants less than 12 weeks of age and randomly assigned them to start ART immediately or defer therapy for 1–2 years. It was halted after an interim analysis revealed a 75% reduction in mortality in the immediate therapy arm (abstract WESS103). In adults, there is mounting evidence that ART should be initiated earlier than is recommended by the current guidelines (at CD4 T cell counts of 200–350 cells/μL),3 and new analyses of the landmark SMART (Strategies for Management of Antiretroviral Therapy) study4 found that patients who interrupted ART, even with a relatively intact immune system, were at increased excess risk of serious illness such as AIDS-defining conditions, malignancy and death from a number of causes including liver and cardiovascular disease, malignancy and AIDS. After several years in which a cautious approach held sway, the pendulum now seems to be swinging back to earlier initiation of treatment. The immunological rationale for this has become clearer: the newer treatments are less toxic so can be taken for longer without the severe side effects of the older agents, and there is an increasing recognition of the public health benefit of early treatment in reducing infectiousness through viral suppression. Biomedical preventionThere was much to discuss in the field of biomedical prevention, as the past year has witnessed some outstanding successes as well as some major setbacks. In a compelling plenary address, Robert Bailey (Professor of Epidemiology, School of Public Health, University of Illinois, Chicago, USA) reviewed evidence from recent randomised trials of the strong protective effects of male circumcision against HIV acquisition (abstract TUPL101). While urging rapid scale-up in high prevalence settings, Bailey cautioned that circumcision needs to be integrated with broader HIV prevention strategies. Observational studies in Sydney (abstract WEAC103) and Peru (abstract WEAC102) showed no significant protective effect of circumcision in gay men. The MIRA (Methods for Improving Reproductive Health in Africa) trial of female diaphragms in African women was concluded with a finding of no benefit (abstract WESS304). Retention rates were high in this long-term study (abstract TUAC104), but low adherence and reduced condom use in the diaphragm arm may have limited the study’s ability to detect an effect. Similarly, no impact on HIV incidence was seen in a trial of daily acyclovir to suppress herpes simplex virus type 2 conducted among women in northern Tanzania (abstract MOAC104), although adherence may have also played a role in compromising the results of this study. The conference heard new details about the two Phase III trials of cellulose sulfate gel as a vaginal microbicide which were suspended early this year. One trial, conducted in Africa and India, was halted after interim analyses revealed a more than twofold increased risk of HIV seroconversion among women using the gel, for reasons which remain unclear (abstract WESS301). The second trial was stopped, even though no differences in risk had been observed (abstract WESS302). At the other end of the development pathway, a Melbourne-based biotechnology company found that its candidate microbicide, SPL7013 gel, was well tolerated in a penile application safety study, paving the way for trials in sexually active women (abstract TUAC1LB). Preventing maternal HIV transmission continued to advance with the finding from Tanzania (abstract TUAX101) and Rwanda (abstract TUAX102) that fewer than 1% of infants whose mothers received postpartum ART were infected with HIV during the breastfeeding period. Supported by recently issued guidelines from the WHO and the United States Centers for Disease Control and Prevention, provider-initiated testing programs have increased the numbers of people tested in the US (abstract TUSY203) and Botswana (abstract TUSY205), and rapid testing has facilitated the return of results (abstract TUSY203). There is nevertheless ongoing controversy about this approach because of its “opt out” nature, particularly in settings where HIV-related stigma, discrimination and limited access to treatment remain realities. Despite the undeniable importance of sexual transmission of HIV globally, intravenous drug use accounts for 10% of the global burden of HIV infection and is the leading mode of exposure in parts of Asia and eastern Europe. Data from Australia showed low and declining HIV prevalence among intravenous drug users, confirming our success in averting an epidemic in this population (abstract MOAC202) through harm-reduction strategies, particularly needle and syringe distribution. Thomas Kerr (Assistant Professor, British Columbia Centre for Excellence in HIV/AIDS, Vancouver, Canada) also reported a strong relationship between efforts to decentralise the distribution of clean needles and syringes and reduced HIV injection risk behaviour in Canada (abstract MOAC205). However, a powerful presentation by Mauro Guarinieri (Chair of the Global Board of the Global Network of People Living with HIV/AIDS) reminded us that such strategies remain largely unavailable in many regions, and that the emphasis on drug prohibition has led to human rights violations and continues to impede efforts to prevent HIV among people who inject drugs (abstract TUSY303). A safe and effective prophylactic vaccine remains the best hope for HIV prevention in the long term but seems as elusive as ever. Ongoing Phase IIb vaccine studies (abstract MOBS301-4) are investigating candidates that boost cellular immune responses and are expected to work by controlling HIV disease progression in those who become infected. The public health benefits of such vaccines could nevertheless include lower rates of illness, reduced potential for HIV transmission, and prolongation of the time to ART initiation. “Lessons learned” from HIV prevention trials were also shared at the conference, with presentations reporting that willingness to participate in trials does not necessarily translate into participation (abstract TUPDC01), and that providing information to trial participants in a focused, locally appropriate manner and within a continuous informed consent framework improves comprehension and message retention (abstract MOAC303). Susan Kippax (Director, National Centre in HIV Social Research, University of New South Wales, Sydney, Australia) reminded us that there are many areas in which further research is needed, including the meanings attributed to prevention technologies, expectations in relation to their effectiveness, and the impact of new and generally experimental prevention technologies on older, proven ones, such as condoms (abstract TUSY302). Basic scienceHIV immunopathogenesis represents a complex interplay between the virus and the host’s immune response, and presentations from Michael Lederman (Director, Center for AIDS Research, Case Western Reserve University, Cleveland, USA; abstract MOPL102) and Jason Brenchley (Research Fellow, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, USA; abstract TUSY402) crystallised current knowledge in this area. The pivotal event early in HIV infection is the massive depletion of mucosal CD4 + T cells that results in immunological and physical damage to the gastrointestinal tract, leading in turn to leakage of components from normal gut microorganisms into the blood. These microbial products stimulate the production of inflammatory cytokines from cells of the innate immune system, triggering T cell activation and expansion, and creating a greater pool of target cells to support HIV replication, ultimately resulting in the depletion of CD4 + T cells and lymph node fibrosis. Strategies to prevent immune activation are now being pursued in order to limit this HIV-mediated damage. An area of intense investigation, critical for developing successful microbicides, is mucosal immunity. A study presented by Dr Maddy Hayes (St George’s University of London, UK) demonstrated using human cervicovaginal tissue that a protein with anti-HIV properties could be elicited from these tissues by a mechanism that is independent of triggering known Toll-like receptors in cells of the innate immune system (abstract MOPDA02). This study raises the possibility of inducing endogenous antiviral factors as mucosal stimulants of the innate immune response. In a macaque study, Eric Arts (Assistant Professor, Division of Infectious Diseases, Case Western Reserve University, Cleveland, USA) demonstrated for the first time that a vaginally applied candidate microbicide (abstract PSC-RANTES) could select for a drug-resistant virus (abstract WESS303). Major implications of this study include the possibility that agents with different drug-resistance profiles should be considered for therapy versus prevention, and the importance of using a combination of drugs in topical microbicides to limit the emergence of HIV drug resistance. The session on new drug targets and compounds highlighted novel approaches for inhibiting HIV replication. Orally bioavailable fusion inhibitors have been identified that have mechanisms of action unlike that of enfuvirtide, the first and currently only available drug in this class (abstract MOPDX01). A novel inhibitor, BIT225, developed by an Australian company, specifically inhibits HIV replication in macrophages, which represent a reservoir for HIV (abstract MOPDX06). An exciting HIV gene therapy approach using a “triple-R” vector was also presented by John Rossi (Professor and Chair of the Division of Molecular Biology, Beckman Research Institute, California, USA). This vector expresses a combination of three types of RNA to target essential viral genes and inhibit expression of the CCR5 host cell receptor, which is critical for viral entry (abstract TUPL102). ConclusionsThe Sydney conference provided an important opportunity for delegates from Australia and the region to participate in an international forum. Treatment access is expanding steadily but encountering practical barriers, and prevention science is entering a new era, with results from recent trials raising complex implementation issues. In the absence of substantial increases in investment in both research and community building, the efficacy–effectiveness gap is likely to remain very wide. As we look forward to the 5th International AIDS Society Conference in South Africa, we would do well both to put the Sydney Declaration into practice and to heed the words of Maura Elaripe, of Igat Hope, the national network of HIV-positive people in Papua New Guinea, at the conference opening ceremony: “Talk with us, not about us”. The Sydney Declaration: good research drives good policy and programming — a call to scale up research1* Ten per cent of all resources dedicated to HIV programming should be used for research towards optimizing interventions utilized and health outcomes achieved. The evolution of HIV prevention, treatment, and care over the past quarter century is one of the great successes of medical science. Committed and sustained research efforts have provided the evidence on which approaches to programming are based. These same scientific efforts are now resulting in new prevention technologies and drugs, and new strategies to manage and deliver both. Good research drives good policy. In recent years, resources have dramatically increased for delivery of existing interventions in resource-limited settings. Although funding remains insufficient to meet the increasing need for services, it is imperative that the global community does not lose sight of the future while responding to the immediate crisis. An effective response to HIV/AIDS requires a sustained commitment to ensure that interventions and approaches to service delivery are continuously improved over time. For example, as current first-line antiretroviral regimens become increasingly available in resource-limited settings, there is an urgent need to identify optimum, durable, and well-tolerated standardised first-line and second-line regimens, and to monitor and respond to resistance patterns as they emerge. Outcomes will not necessarily be the same in diverse settings across the globe. Operations research is critical, in addition to basic, clinical, prevention, social, and policy research. We must identify which approaches are effective in the field, which are not, and why. We must also learn how to integrate HIV-specific services with primary, tuberculosis, malaria, prenatal and postnatal, and sexual and reproductive health services. None of these services have been as effectively linked to scale-up of HIV programming as is possible or necessary. Furthermore, greater understanding of the social, political, and cultural barriers that perpetuate stigma and discrimination can contribute to ensuring that governments act in the interests of public health. Operations research will enable rapid implementation of new technologies to prevent, diagnose, and treat HIV infection, and can help to ensure that health systems are strengthened as a result of scaling-up HIV prevention, treatment, and care. Unfortunately, few granting agencies or national health budgets commit designated funds to operations research, and where such funding is available, it is often underused. The Global Fund to Fight AIDS, Tuberculosis and Malaria, for example, allows up to 10% of each grant to be allocated for operations research, but this provision is rarely used by countries and the research community is rarely represented on Country Coordinating Mechanisms (CCMs). The lack of participation on CCMs further reduces the likelihood that operations research will be a priority in funding applications. An ancillary benefit of integrating research into the overall approach to scale-up in the developing world will be an expanding cadre of health-care workers trained in research methodologies and practice. Such research should not be seen as an additional burden on the various funding bodies or ministries of health but, on the contrary, as the only means by which we can refine our understanding of what is and is not effective. Last but not least, all areas of research can further strengthen the efforts of the global AIDS community to confront the absurd theories of AIDS denialists as well as the “magic” cures that continue to confuse policymakers, health-care professionals, and communities of people at risk of and living with HIV/AIDS throughout the world. HIV professionals must continuously build on the evidence base to ensure sound and effective policies and practices in HIV/AIDS prevention, treatment, and care. The undersigned individuals and organisations call on national governments and bilateral, multilateral, and private donors to allocate 10% of all resources for HIV programming to research. We believe that without such funding we will fail to maintain a sustained and effective response to the AIDS pandemic. * As of 15 August 2007, there were 1854 signatories to the Sydney Declaration.

Lisa Maher PhD · Gilda Tachedjian BSc(Hons), PhD · Jennifer F Hoy FRACP · Iona Millwood PhD · Rebecca J Guy BAppSc, MAppEpid · Nick M Walsh MB BS, MPH · John J Zaunders BSc, PhD · Anthony Jaworowski BSc(Hons), PhD · John M Kaldor PhD

To the Editor: Influenza experts have warned of the possibility of an influenza pandemic, and planning for such an event is underway.1,2 The provision of health care during a pandemic will pose particular challenges. Health care workers will be at risk of exposure, and will become ill at rates similar to those for the general population. Compounding inevitable staff shortages will be health care workers absent from work because of a need to care for dependents or fear of catching influenza. Prompted by discussions on an appropriate response to pandemic influenza, we solicited opinions from employees within our network (including medical, nursing, clinical support, catering and administrative staff) about their attitudes to working during a pandemic. Between 1 February and 30 April 2007, a survey that could be self-administered and completed anonymously was placed on our hospital intranet. Our staff were advised of its presence by email and through advertising on the intranet. The survey could also be completed when attending for influenza vaccination. Participants could complete surveys directly onto an electronic database, or return them to the investigator. We received 1440 completed surveys, including those from 137 medical staff (10%), 628 nursing staff (43%), and 352 clinical support staff (25%). The overall response rate was approximately 14% (1440/10 000). The mean age of respondents was 42 years (range, 18–73 years); 83% were female and 36% had dependent children. Overall, 74% agreed they needed more education on pandemic influenza (medical staff, 66%; nursing staff, 78%; P = 0.025) and 48% believed a pandemic would occur in the next decade (medical staff, 39%; nursing staff, 52%; P = 0.025). Sixty-seven per cent stated they would be available to work during a pandemic; 26% (medical staff, 18%; nursing staff, 27%; P = 0.05) stated they would stay home to care for dependents, while 10% admitted they would stay away because of fear of catching influenza. Most employees expected to be provided with personal protective equipment (92%), antiviral medications (90%) and vaccine (89%). Sixty-four per cent believed the hospital should supply their families with antiviral medications, and 63% thought their families should receive vaccine. Twenty per cent believed they would require a place of residence while working during a pandemic (medical staff, 32%; nursing staff, 24%; P = 0.05), 45% were prepared to be relocated to another site (medical staff, 58%; nursing staff, 40%; P < 0.001) and 36% were prepared to change to another duty (medical staff, 30%; nursing staff, 39%; P, not significant). Our survey has highlighted areas that may need attention in preparing for a pandemic. As a minimum, we believe targeted education is required now for all health care workers who will be expected to work during a pandemic. Our ability to cope will depend on the depth of our preparation.

Rhonda L Stuart · Elizabeth E Gillespie

An obscure Portuguese document from 16th century Indonesia describes an illness that destroyed poultry before devastating the human population of the region. The cause of the illness remains unresolved; it may have been infectious or non-infectious. Isolation of the region because of trading practices probably prevented spread of the illness, reinforcing the value of quarantine or isolation as a public health measure The following extract comes from an unsigned treatise written by António Galvão, captain from 1536 to 1539 of the Portuguese fortress on the island of Ternate in the Maluku archipelago, in what is now Indonesia (Box): At the end of April 1539 there appeared in Ternate and throughout this region a star in the west, with many enormous rays like a natural torch, similar to the one that was seen in Portugal when the earth shook. It lasted throughout May and June. With the south winds came this sickness to Bacan; before long it spread throughout all the islands beginning in the chickens. Because it happened one morning that more than 50 or 60 chickens belonging to António Galvão which had been growing healthy and fat were found dead; and afterward more than 110 of his people, both servants and slaves, fell ill, not one being spared and the more part dying on him, not counting the Portuguese and their children; and this evil was so common throughout all the land that they could not bury them, and the sea was full of the dead, and many places were depopulated, and thus they found themselves in visions at night for the men were amazed, saying that they had never before seen such a thing, nor had they heard of it from their ancestors [translation by Brett Baker].1 Although from ancient times it was traditional for authors to begin the description of any epidemic with the death of birds,2 we believe that Galvão’s description was a true reflection of the events rather than a stylistic convention. Galvão made no mention of bird deaths when describing “an illness like the plague” that occurred 5 years earlier;1 therefore, his description of dying chickens in 1539 is likely to truly reflect what happened. The 1539 epidemicIt appears that a disease rapidly destroyed a group of 60 healthy chickens and was followed soon after by a disease of similar lethality in humans, affecting the indigenous population, slaves and the Portuguese. The striking features of this outbreak are its rapidity, severity, probably its mortality rate (although this cannot be determined) and the fact that, as it spread throughout the archipelago, it always seems to have been preceded on each island by poultry deaths. Galvão states that whole regions were depopulated. However, he may have exaggerated this. Only 7 years later, Europeans commented repeatedly on the high populations they found there, describing Ambon as “densely populated”.3 Still, it seems that the illness killed large numbers of people throughout the islands over a relatively short period. Galvão and the indigenous population did not recognise the illness, although devastating epidemics of unspecified diseases “raged through the islands every 7 or 8 years”.4 The possible causes could be infectious or non-infectious. Possible infectious causesInfections in chickens and humansIt seems unlikely that two separate and lethal infections devastated chickens and humans almost simultaneously; therefore, a single responsible agent is more probable. Newcastle disease can kill chickens rapidly but does not cause disease in humans.5 Psittacosis can infect domestic poultry6 and then humans; however, the rapidity and lethality of the disease in 1539 in both chickens and humans is not typical of psittacosis. Anthrax is a devastating zoonosis most typically associated with herbivores. Infection of birds with anthrax is usually asymptomatic and is detected by spores shed in faeces.7 Chickens, especially, seem resistant to the disease.8 Could avian influenza have caused the 1539 outbreak? In modern times, the H5N1 strain of avian influenza affects birds and humans, with human-to-human transmission considered to be very rare. In the current climate, one would have to consider avian influenza as a differential diagnosis for an infection targeting both domestic poultry and humans. Few zoonoses other than H5N1 influenza kill both. Features of the 1539 outbreak have some similarity to avian influenza of the 21st century. The infection appeared to be an emerging infectious disease, not seen before by the indigenous people or the Portuguese. Also, throughout the islands, the illness seemed to affect poultry before affecting humans, supporting the idea of poultry-to-human transmission. However, there are strong arguments against avian influenza being responsible for the 1539 outbreak. First, the large number of human casualties is in direct contrast to the situation in the 21st century. In today’s H5N1 outbreaks, human death rates are low, despite the exposure of large populations to chickens.9 This may be attributable to the H5N1 virus binding only to galactose receptors in the lower respiratory tract, unlike human influenza viruses, which can bind to galactose receptors in the upper respiratory tract.10 Therefore, if avian influenza was the cause of the 16th century epidemic, the degree of human devastation described is surprising, even if Galvão exaggerated the situation. An avian influenza virus capable of human-to-human transmission might explain so many human deaths, but a mutation rapid enough to allow this is questionable. Also, H5N1 influenza in humans has a distinct clinical syndrome of focal respiratory symptoms often accompanied by diarrhoea,9 yet Galvão did not describe focal features of the 1539 outbreak. One could attribute this to a failure to record the symptoms for one reason or another, but this seems not to have been the case. The treatise elsewhere is filled with details and elaborate descriptions by Galvão, including careful depictions of the clinical features of other epidemics and illnesses.1 Therefore, it is more likely that the 1539 illness truly lacked obvious focal clinical features, possibly because of its rapid and severe course, but this would certainly make avian influenza far less likely as a diagnosis. The role of the monsoonAlthough the specific organism cannot be pinned down, the way in which the illness appeared to spread through this group of islands but not outside it also supports an infectious aetiology if the trading practices of the region are studied. Strong monsoonal patterns strictly regulated the periods of external contact. At the time of year during which the outbreak occurred, there would have been trading only among the islands but not outside them. Generally speaking, sailing vessels from outside the region could arrive in the archipelago only twice each year during rather narrow windows of time. Most ships approached via the Java and Banda Seas, arriving in the southern part of the archipelago about mid February. Those approaching from the north would arrive around the end of October. Regardless of when or by which route they had arrived, all sailing vessels had to depart from the Maluku archipelago via the southern route with the arrival of the south-east monsoon, about the middle of May.11 This monsoon is the “south winds” identified by Galvão as having marked the advent of the illness in Bacan. Consequently, the outbreak would have begun just as external trading vessels were departing from the island of Ambon about 350 km to the south, and it would be more than 5 months before the first outside ship could return to Maluku, presumably after the infection had run its course. At the same time, traffic among the islands in the Maluku region would have continued without interruption. This was possible because korakoras and other native craft could be rowed in shallow, reef-infested seas regardless of the prevailing winds. Constant inter-island trade was necessary because so many of the spice-producing islands depended on imported foodstuffs. Bacan, where this illness was first observed, produced no food of its own and therefore relied entirely on supplies brought in from other islands, and Ternate was in almost the same situation.4 These inter-island food shipments would have included chickens.12 Chickens were imported from a handful of fertile areas within the Maluku region rather than raised locally;13-15 therefore, local inter-island trade in chickens would have been sufficient for an infection carried by fowl to “spread through all the islands”.1 Possible non-infectious causesCauses of the illness other than infection could include environmental agents, especially foodborne or gaseous substances. Claviceps purpurea is a fungus that contaminates rye-based foods primarily, resulting in outbreaks of epidemic ergotism with mortality rates of 10%–20%. Epidemic ergotism has been well documented from medieval times,16 so its distinct clinical syndromes (limb gangrene or recurrent abnormal posturing) would have been recognised and recorded by Galvão. In Lake Nyos, Cameroon, in 1986, 1700 people and 3000 cattle mysteriously and suddenly died. Eventually, the culprit was found to be the massive release of carbon dioxide from crater lakes.17 It is unlikely, though, that any toxin came from the “star in the west” that Galvão described. Astronomical records confirm that a comet was visible in the sky in May 1539, indicating that Galvão’s star was probably a comet in space rather than a meteorite entering the atmosphere bringing a deadly toxin.18,19 Yet, the most compelling argument against a foodborne or gaseous agent is Galvão’s observation that chickens were consistently affected before humans, not just in Bacan, but in all the islands of the Maluku region.1 A zoonosis seems more plausible. Lessons for modern-day quarantineAlthough the 1539 outbreak was probably not avian influenza, it is surprising that, given the current avian H5N1 pandemic, a passage about a devastating illness in poultry and humans from the 16th century has not been discussed recently. Galvão’s treatise has been available in published form with a parallel English translation since 1971. As part of the Jesuit Historical Institute’s Sources and studies for the history of the Jesuits series, it has likely reached a narrow and rather specialised audience, one that, until recently at least, may have skipped over the importance of an illness that appears to have affected both chickens and humans. In conclusion, the devastating illness occurring in north-east Indonesia in the 16th century, affecting first chickens and then humans, is consistent with a zoonosis. The 16th century outbreak probably failed to spread because of the isolation of the islands from the rest of the world through climate-determined trading patterns. This reinforces the value of (even unintentional) quarantine or isolation as a public health measure. Given the ease of global movement of people, animals and cargo in the modern era, its enforcement will now be a far greater challenge. Location of the 1539 epidemic The northern islands of the Maluku archipelago in Indonesia.

Sanjaya N Senanayake BSc(Med), FRACP, MAppEpi · Brett C Baker MA

A 35-year-old man presented after a generalised tonic–clonic seizure. He had a 6-month history of intermittent headache and vertigo but no previous seizures. An electroencephalogram showed diffuse slowing, indicating the postictal period. Axial contrast-enhanced computed tomography (CT) showed multiple cystic lesions scattered throughout the brain parenchyma, many containing dense white inclusions with a typical appearance of scoleces (tapeworm attachment organs), consistent with a diagnosis of neurocysticercosis (Figure). Serum was positive for cysticercus IgG antibodies by ELISA (enzyme-linked immunosorbent assay) (1.68 optical density [OD] units; reference range, < 0.9 OD units). Stool examination failed to show eggs of Taenia solium. There was no evidence of cysticerci in thighs, subcutaneous tissues or in the posterior segment of the eye on fundus examination. The patient was treated with antiepileptic drugs, glucocorticoids and albendazole (15 mg/kg/day for 21 days). He remained seizure-free and was advised to have a repeat CT scan after 12 weeks.

Vinay Kapur · Jeet Ram Kashyap · Ravinder Kaur · Atul Sachdev

Objective: To evaluate a hospital-wide surveillance and intervention program introduced to reduce the incidence of bloodstream infections (BSIs) caused by intravascular (IV) catheters.Design, setting and participants: Prospective surveillance of all inpatients and outpatient attendees with positive blood cultures (both hospital-onset and community-onset) at a 500-bed tertiary referral hospital from 1998 to 2005.Interventions: Prompt review of all positive blood cultures with identification of BSIs due to IV catheters and associated preventable factors; weekly team meetings and regular reports to clinical areas, with assistance to implement targeted interventions.Main outcome measure: Number of BSI episodes due to IV catheters per year.Results: There were 491 BSI episodes due to IV catheters, mainly central venous catheters. Episodes per year fell from 110 in 1998 to 48 in 2005 (from 32% of all BSI episodes to 14%; a > 50% reduction). From 1998 to 2005, the rate per 1000 discharges fell from 2.3 to 0.9 (P for trend < 0.0005) and the rate per 1000 patient-days fell from 0.6 to 0.3 (P for trend < 0.0005).Conclusions: Our program was associated with a profound drop in the number of IV catheter-related BSIs per year. Active surveillance and intervention programs can lead to substantial and sustained reductions in these common life-threatening infections.

Peter J Collignon FASM, FRCPA, FRACP · Dianne E Dreimanis BHSc(Nursing), MN · Wendy D Beckingham RN, BHSc(Nursing) · Jan L Roberts RN, BHSc(Nursing) · Anne Gardner BA, PhD

Objective: To document the epidemiology, clinical characteristics and diagnosis of an outbreak of Mycobacterium ulcerans infection (Bairnsdale or Buruli ulcer [BU]) during the period 1998–2006, and compare delays in diagnosis between residents of endemic and non-endemic regions.Design and setting: Retrospective case study of patients identified through infectious disease physicians on the Bellarine Peninsula and the Victorian Department of Human Services notifiable diseases database.Main outcome measures: Description of events leading to diagnosis of BU.Results: Eighty-five BU patients recalled their experience. Fifty-three patients were older than 60 years, and 61 permanently resided on the Bellarine Peninsula. The onset of symptoms occurred most frequently in mid winter. Twenty-eight patients had lesions on the arm and 51 on the leg. The median time between onset of symptoms and first medical contact was shorter for those living in the endemic area (3.0 weeks; interquartile range [IQR], 1.0–5.0 weeks) compared with non-endemic areas (5.3 weeks; IQR, 2.0–9.5 weeks) (P = 0.05). Patients who resided in the endemic area had a shorter median time from their first medical appointment to diagnosis (1.0 week; IQR, 0.0–3.9 weeks) than those who resided in non-endemic areas (5.0 weeks; IQR, 1.3–8.0 weeks) (P = 0.001).Conclusion: Delay in presentation and time to diagnosis of BU are longer in non-endemic than endemic areas. Measures should be taken to raise awareness of the disease in non-endemic areas.

Tricia Y J Quek BSc(Hons) · Margaret J Henry BSc(Hons), PhD · Julie A Pasco BSc(Hons), PhD · Daniel P O’Brien MB BS, FRACP · Paul D R Johnson PhD, FRACP · Andrew Hughes MB BS(Hons), FRACP · Allen C Cheng FRACP, PhD · Jane Redden-Hoare BN(Hons), PhD · Eugene Athan MB BS, FRACP

To the Editor: A 30-year-old man presented with pain, swelling and discharge from lesions on his left arm. He had undergone extensive tattooing on the arm 3 days earlier at a commercial tattoo operation, where single-use needles were used, with initial drawing of lines followed by additional shading. The patient complained of severe neuropathic pain in the arm, which was greater than would be expected from uncomplicated bacterial cellulitis. He did not give a history of oral or genital herpes and had previously been tattooed without complication. On presentation, the patient had a low-grade fever (37.9°C), a heart rate of 80 beats/min and blood pressure of 130/80 mmHg. He had no neurological deficit. Vesicular lesions were visible in the region of the tattoo marks, predominantly affecting areas of shading and with minimal spread outside tattooed areas (Box). A bacterial swab of the lesions grew methicillin-sensitive Staphylococcus aureus, and a polymerase chain reaction test of vesicular fluid was positive for herpes simplex virus type 1 (HSV-1). The patient was commenced on intravenous flucloxacillin (1 g four times daily) and oral famciclovir (250 mg three times daily). He required ongoing inpatient management for pain relief. Five days after development of the lesions, HSV-1 serology demonstrated positive results for IgM and IgG. An HIV test was negative. The patient’s lesions slowly resolved, and he was discharged 7 days after admission. Most concerns regarding infectious complications of tattooing have focused on transmission of blood-borne viruses, but superficial infections with other pathogens have also been described.1 The personal care and body art industries are regulated in Australia to minimise the transmission of blood-borne infection,2 and most state and territory authorities also publish infection control guidelines. Herpes dermatitis is often confused with bacterial infection, although co-infection may occur. This distinction is clinically important, as antibiotics and surgical debridement are not usually required for herpetic infections, and herpetic lesions may recur. Secondary herpetic infection complicating skin disease is most commonly associated with eczema (eczema herpeticum) or other skin diseases (Kaposi’s varicelliform eruption), and minor skin trauma, such as in herpetic whitlow or herpes gladiatorum.3,4 We are not aware of any previous reports of herpetic infection complicating tattoo placement. The distribution of herpetic lesions in our patient suggested that the needle used for tattoo shading became contaminated with HSV-1 during the course of tattoo placement, but it is also possible that superinfection occurred through damaged skin after the procedure. We propose the term “herpes compunctorum” to describe this condition. Vesicular lesions on patient’s tattooed forearm

Catherine S Marshall · Felicity Murphy · Shannon E McCarthy · Allen C Cheng

Objective: Design and setting: Analysis of national surveillance system data for 1993–2006.Main outcome measures: Number and population rate of new HIV diagnoses by year, exposure route and demographic characteristics.Results: Between 1993 and 2006, 12 313 new diagnoses of HIV infection were reported in Australia. From 1993 to 1999, the annual number of diagnoses declined by 32% from 1056 to 718, and then increased by 31% from 763 in 2000 to 998 in 2006. Between 2000 and 2006, diagnosis rates significantly increased in Victoria, Queensland, South Australia and Western Australia. The most frequent route of HIV exposure was male-to-male sex, accounting for 70% of diagnoses. Heterosexual contact accounted for 18% of cases, with just over half of these people born in or having a sexual partner from a high-prevalence country. Exposure by injecting drug use remained infrequent.Conclusions: The number of HIV diagnoses has risen in the past 7 years, but not in New South Wales, which has long had the highest rates. The differences in rates between states/territories are likely to be due to divergent trends in sexual risk behaviour in men having male-to-male sex, which remains the predominant route of HIV transmission in Australia. There is a need for effective, innovative and evidence-based programs for HIV prevention, particularly among men having male-to-male sex.

Rebecca J Guy BAppSc, MAppEpid · Ann M McDonald BSc, MPH · Mark J Bartlett RGN, MPH, MAppEpi · Jo C Murray RN, GradDipNursing · Carolien M Giele RN, DipClinEpi, MPH · Therese M Davey DipHealthCounselling, DipClinEpi · Ranil D Appuhamy BSc, MB ChB, MIntPH · Peter Knibbs RN, DipAppSci(Nursing) · David Coleman BSc(Hons), DipAppSci · Margaret E Hellard FRACP, FAPHM, PhD · Andrew E Grulich MB BS, PhD, FAFPHM · John M Kaldor PhD

The four main classes of antifungal drugs are the polyenes, azoles, allylamines and echinocandins. Clinically useful “older” agents include topical azole formulations (for superficial yeast and dermatophyte infections), first-generation triazoles (fluconazole and itraconazole, for a range of superficial and invasive fungal infections), amphotericin B formulations (for a broad range of invasive fungal infections) and terbinafine (for dermatophyte infections). Clinically important “newer” agents include members of the echinocandin class (eg, caspofungin) and second-generation triazoles (eg, voriconazole and posaconazole). Voriconazole and posaconazole have broad-spectrum activity against yeasts and moulds, including Aspergillus species. Posaconazole is the only azole drug with activity against zygomycete fungi. Caspofungin and the other echinocandins are effective in treating Candida and Aspergillus infections. The azoles are relatively safe, but clinicians should be aware of drug–drug interactions and adverse effects, including visual disturbances (with voriconazole), elevations in liver transaminase levels, and skin rashes. Caspofungin has minimal adverse effects. Combination antifungal therapy may be appropriate in selected patients with invasive fungal infections, but is empiric and driven by individual physician practice.

Sharon C A Chen PhD, FRACP, FRCPA · Tania C Sorrell MD, MB BS, FRACP

Clinical records Patient 1 A 27-year-old man presented to an infectious diseases outpatient clinic in May 2006 with a 3-month history of nocturnal dry cough, paroxysmal dyspnoea, malaise and unintentional weight loss of 5 kg. He had previously presented to a general practitioner and was treated with two courses of antibacterial drugs without a decrease in symptoms. He had no significant past history of chronic respiratory illness or tuberculosis, was a non-smoker and had been working in Australia for 5 years. He was born in India and had recently returned there on a holiday to visit family and friends. Physical examination, including respiratory system examination, was unremarkable. Full blood examination revealed marked eosinophilia (28.8 × 109/L; reference range [RR], 0.0–0.5 × 109/L). A chest x-ray and computed tomography (CT) showed a diffuse, bilateral fine micronodular pattern throughout both lung fields (Figures A and B). The patient had a raised serum IgE concentration of 24 020 kU/L (RR, 0–120 kU/L), and was positive for filarial IgG by enzyme immunoassay, but negative for filaria on a midnight blood smear. Strongyloides serological tests were also positive, but treatment with two doses of ivermectin did not resolve the nocturnal cough. Three stool specimens were examined for helminths, all of which were negative. The patient was given antifilarial treatment with diethylcarbamazine (150 mg three times daily) for 14 days. Symptoms decreased rapidly, and the eosinophil count was nearly normal (2.7 × 109/L) by 4 weeks. Tropical pulmonary eosinophilia was diagnosed on the basis of the clinical syndrome, positive serological results for filaria, exclusion of other parasitic infections and successful clinical response to a trial of antifilarial treatment. Patient 2 A 25-year-old woman from Sri Lanka presented to the Royal Melbourne Hospital emergency department in September 1994 with a 3-day history of productive cough, pleuritic chest pain and increasing exertional dyspnoea. She had arrived in Australia 6 months previously. Empirical treatment with salbutamol and doxycycline prescribed by her GP had not decreased the symptoms. Examination revealed scattered bilateral expiratory wheezes. A full blood examination revealed an eosinophil count of 21.5 × 109/L, and the initial chest x-ray showed diffuse pulmonary infiltrates, which were confirmed on CT. A bronchoscopy was performed to investigate these pulmonary lesions, which showed pus cells but no visible parasites. An open lung biopsy was then performed, before knowledge of relevant serological results, which revealed an eosinophilic infiltration of the alveolar spaces, suggestive of an eosinophilic pneumonia (Figures C and D). Results of other investigations included three negative stool specimens, a strongly positive serological result for filaria, negative blood film for microfilariae, and a raised serum IgE concentration (28 400 kU/L). Serological tests for schistosomiasis and strongyloides were also both positive at low titres. Given the marked eosinophilia, widespread chest infiltrates and strongly positive filarial serological result, the most likely diagnosis was thought to be tropical pulmonary eosinophilia. The patient was treated with diethylcarbamazine (100 mg three times daily) for 21 days. After some initial nausea, her symptoms decreased, and the eosinophil count was resolving (0.7 × 109/L) by 8 weeks after treatment. Patient 3 A 30-year-old man from India presented to an infectious diseases outpatient clinic via migrant screening in October 2006 with an abnormal appearance on chest x-ray, which showed fine reticulonodular opacities throughout both lung fields. The patient was born near Calcutta and had arrived in Australia 3 months previously. He was a non-smoker and reported a history of non-productive cough over several days. Physical examination was unremarkable including the respiratory system examination. A full blood examination revealed eosinophilia (13.0 × 109/L) and a positive serological result for filarial IgG. Results of other investigations included a raised serum IgE concentration (> 5000 kU/L), a positive serology result for strongyloides and negative serology results for schistosomiasis and toxocara, a negative immunochromatography result for Wuchereria bancrofti, and three negative stool specimens to particularly exclude strongyloides. A blood film did not show microfilariae. Pulmonary function tests showed moderate restriction (forced vital capacity, 3.0 L, or 67% of reference range) without obstruction and normal gas transfer. The patient was initially treated for strongyloides infection with ivermectin, but the eosinophilia persisted. Diethylcarbamazine (150 mg three times daily) was given for 14 days. Within 2 weeks, the eosinophil count had dropped to 1.0 × 109/L. The patient was clinically well at follow-up 3 months later. A: Patient 1 — chest x-ray showed diffuse fine nodules. B: Patient 1 — computed tomography showed a widespread, bilateral fine micronodular pattern. C, D: Patient 2 — low and high magnification (× 200 and × 400) views of a lung biopsy specimen showed eosinophilic infiltration of alveolar spaces (haematoxylin and eosin stain). Tropical pulmonary eosinophilia is a rare but well recognised syndrome characterised by pulmonary interstitial infiltrates and marked peripheral eosinophilia. We report three cases of this syndrome presenting with cough in immigrants to Australia, to highlight awareness of this treatable infectious disease. This condition is more widely recognised and promptly diagnosed in filariasis-endemic regions, such as the Indian subcontinent, Africa, Asia and South America. In non-endemic countries, patients are commonly thought to have bronchial asthma.1,2 Chronic symptoms may delay the diagnosis by up to 5 years.1 Early recognition and treatment with the antifilarial drug, diethylcarbamazine, is important, as delay before treatment may lead to progressive interstitial fibrosis and irreversible impairment.3 Lessons from practice Tropical pulmonary eosinophilia should be considered in patients who have lived in filaria-endemic countries, such as the Indian subcontinent, and present with respiratory symptoms and hypereosinophilia. The most common misdiagnosis is asthma, with overlapping symptoms of chronic cough, paroxysmal dyspnoea and wheeze. Early diagnosis and treatment with diethylcarbamazine (DEC) may prevent progressive pulmonary disease. The condition of marked eosinophilia with pulmonary involvement was first termed tropical pulmonary eosinophilia in 1950.4 The syndrome is caused by a distinct hypersensitivity immunological reaction to microfilariae of W. bancrofti and Brugia malayi.3,5 However, only a small percentage (< 0.5%)6 of the 130 million people globally who are infected with filariasis apparently develop this reaction. The clearance of rapidly opsonised microfilariae from the bloodstream results in a hypersensitive immunological process and abnormal recruitment of eosinophils, as reflected by extremely high IgE levels of over 1000 kU/L.3,7 The typical patient is a young adult man from the Indian subcontinent.5 The diagnostic criteria for tropical pulmonary eosinophilia7 include: history supportive of exposure to lymphatic filariasis; peripheral eosinophilia count (> 3 × 109/L); elevated serum IgE levels (> 1000 kU/L); increased titres of antifilarial antibodies; peripheral blood negative for microfilariae; and clinical response to diethylcarbamazine. High antifilarial IgG titres to microfilariae often result in cross reactivity with other non-filarial helminth antigens,8,9 such as strongyloides and schistosoma antigens, as demonstrated in our reported cases. It is important to exclude other parasitic infections before tropical pulmonary eosinophilia is diagnosed, by serological tests, examination of stool specimens in a laboratory experienced in parasitic infections, or a trial of antihelminth medication. Other parasitic infections, such as the zoonotic filariae, dirofilariasis, ascariasis, strongyloides, visceral larva migrans and hookworm disease, may also be confused with tropical pulmonary eosinophilia because of overlapping clinical features, serological profile and response to diethylcarbamazine3,7,9,10 (Box 1). Radiological findings are non-specific, with normal appearance on chest x-ray in up to 20%.5 Although lung biopsy was performed in Patient 2, it is not part of the routine diagnostic work-up of tropical pulmonary eosinophilia. No universal treatment guidelines have been established for tropical pulmonary eosinophilia.1,7 The antifilarial diethylcarbamazine (6 mg/kg/day for 21 days6) remains the main therapeutic agent and is generally well tolerated. Reported side effects include headache, fever, pruritis and gastrointestinal upset.11 The eosinophil count often falls dramatically within 7–10 days of starting treatment.3 Diethylcarbamazine is available only through the Special Access Scheme of the Therapeutic Goods Administration. Symptoms persist after treatment in up to 25% of patients.5 The role of adjunctive therapy with corticosteroids in preventing long-term fibrosis has not been studied. Our three cases demonstrate the variable clinical presentations and symptom duration of tropical pulmonary eosinophilia. With increased travel and migration of patients from filaria-endemic areas, physicians need to remain aware of tropical pulmonary infections presenting with cough, dyspnoea and variable systemic symptoms, as delayed recognition of this uncommon clinical entity may increase morbidity. 1 Characteristic features of parasitic infections with pulmonary symptoms and eosinophilia Condition Parasite Respiratory symptoms Geographical distribution Laboratory diagnosis Treatment Tropical pulmonary eosinophilia Wuchereria bancrofti, Brugia malayi Nocturnal cough, wheeze, dyspnoea Tropical and subtropical areas, especially India and Sri Lanka Serology, blood film, IgE levels Diethyl- carbamazine Strongyloides Strongyloides stercoralis Loeffler’s-like syndrome,* hyperinfection syndrome Tropical and subtropical, including northern Australia Serology, stool Ivermectin Schistosomiasis Schistosoma mansoni, Schistosoma haematobium, Schistosoma japonicum Katayama fever, pulmonary hypertension, cor pulmonale Asia, Africa, South America Serology, stool and urine Praziquantel Ascariasis Ascaris lumbricoides Loeffler’s-like syndrome* Asia, Africa, South America Stool Albendazole Visceral larva migrans Toxocara canis, Toxocara cati Eosinophilic pneumonia, wheeze, dyspnoea Worldwide Serology Albendazole Dirofilariasis Dirofilaria immitis Pulmonary lesion Tropical and subtropical, including Australia Serology None Hookworm disease Ancylostoma duodenale Loeffler’s-like syndrome Tropical and subtropical areas Stool Albendazole * Loeffler’s-like syndrome: transient pulmonary infiltrates and eosinophilia from transpulmonary passage of helminth larvae.

Michelle K Yong MB BS · Caroline L Marshall FRACP · Damon P Eisen FRACP, MD

Three cases of cholera in women aged 71, 72 and 84 years were notified in November 2006 in Sydney, New South Wales. This is the first reported cluster of cholera in Australia for over 30 years, and was an unusual outbreak in patients with no history of recent travel to cholera-endemic areas. A food trace-back investigation found that the only exposure common to all cases was consumption of raw whitebait imported from Indonesia. This outbreak demonstrates that the practice of eating raw whitebait does occur in Australia, albeit in the process of taste-testing uncooked fritter batter. All three patients were undergoing long-term therapy with proton-pump inhibitors, which may have contributed to their susceptibility to the disease. A review of importation practices of food from cholera-endemic regions may be required to prevent future transmission.

Bradley Forssman MB BS, MPHTM, FAFPHM · Trish Mannes BAppSci, MPH · Jennie Musto MPH · Thomas Gottlieb MB BS, FRACP, FRCPA · Graham Robertson MSc · Jonathan D Natoli BSc · Craig Shadbolt PhD · Brian Biffin · Leena Gupta MB BS, MPH, FAFPHM

Re: “Influenza outbreak related to air travel”, by Andrew G Marsden, in the 4 August 2003 issue of the Journal (Med J Aust 2003; 179: 172-173). The title should have been “Outbreak of influenza-like illness related to air travel”, consistent with the text.

Andrew G Marsden

To the Editor: I read with great interest the recent updated review of amoebiasis by van Hal and colleagues1 and their previous letter2 describing three cases of locally acquired amoebiasis due to Entamoeba histolytica in Australian men who have sex with men (MSM). These articles should alert clinicians to the emergence of invasive amoebiasis and the possibility of person-to-person transmission of E. histolytica through oral–anal or oral–genital sex among MSM in developed countries. The same phenomenon has been reported in Taiwan3 and Japan.4 The prevalence or incidence of intestinal amoebiasis among people at risk may have been underestimated in the past, as microscopy of stool specimens has lower sensitivity and specificity than E. histolytica antigen detection methods for diagnosing the disease.1,5 Cases of amoebiasis may evade detection using the diagnostic algorithm proposed by van Hal and colleagues,1 which suggests using microscopy of stool specimens to detect E. histolytica complex followed by confirmation with specific antigen detection methods or molecular methods. To increase diagnostic sensitivity and specificity, I suggest revising the diagnostic algorithm for intestinal amoebiasis in developed countries to include more accurate first-line detection methods. For example, specific antigen detection methods or polymerase chain reactions, as proposed by Tanyuksel and Petri,5 could be incorporated.

Chien-Ching Hung

To the Editor: van Hal and colleagues deserve congratulations for their lucid, concise and timely review of the complex problem of human amoebic infection and its diagnosis.1 Not surprisingly, however, their article raises more questions than it answers. To me, the gist of their message was as follows: what was in the past diagnosed as Entamoeba histolytica infection, based on the microscopic identification of organisms from faeces, culture or histological sections, actually may have been caused by other species, viz. E. dispar (a recently described non-pathogen) or E. moshkovskii (known for a long time from sewage samples, but only recently found to infect humans). Because these species are all identical morphologically, they can be distinguished reliably only by sophisticated molecular techniques. To complicate matters further, despite E. dispar having been virtually defined as the “non-invasive form” of Entamoeba, most true E. histolytica infections are still asymptomatic.2 Not only the parasite, but also individual host factors (perhaps including genetics), determine pathogenicity. Thus, not all people infected with the same pathogenic strain will manifest symptoms or signs of invasive disease. Given their biology and evolution, it is conceivable that, eventually, invasive strains of even E. dispar will be discovered! Furthermore — and this seems not to have been investigated yet — mixed infections involving different species and strains of these parasites almost certainly occur (not to mention the “traditional” non-pathogenic amoebae, which frequently do occur in mixed infections). The authors advocate treatment of even asymptomatic E. histolytica infections, but how would these be detected outside epidemiological surveys or healthy population screening programs? Given the difficulty and expense of specifically identifying the infective organism even in symptomatic cases, and the relative cheapness of treatment, surely it would be sufficient simply to treat on the basis of clinical presentation plus the identification of E. histolytica-like parasites, with or without objective evidence of histopathology. Anything more could be justified only within the context of a well funded and carefully designed research program and/or epidemiological study.

Paul Prociv

In reply: We agree with Hung that molecular and antigen testing methods are more sensitive for Entamoeba histolytica detection than microscopy and that reliance on microscopy alone would result in under-detection. Our algorithm1 was presented the way it was for several reasons. Firstly, both molecular and antigen testing are significantly more expensive than microscopy. Secondly, as these tests can currently only detect a single pathogen, they would not replace microscopy. Most patients, especially men who have sex with men (MSM), have multiple intestinal parasites, so the more specific methods would remain an adjunct in parasite detection.2 Thirdly, the positive predictive value of any test is dependent on the prevalence of the disease. The prevalence of E. histolytica in Australia, based on current data, is less than 1% in high-risk populations, including MSM. Thus, at present, molecular and antigen tests would be more likely to give false positive than true positive results. However, we agree that our algorithm could be modified as suggested if prevalence rates were between 5% and 10%. Finally, as seen in the MSM population in Taiwan, this is not a static situation, and ongoing local surveillance is required.3 We agree with Prociv that, before the introduction of molecular techniques, E. histolytica prevalence would have been overestimated. We also agree that specific host factors and/or undefined parasitic virulence factors can lead to invasive disease. However, given the extensive molecular work that has been undertaken, we believe it unlikely that invasive strains of E. dispar will be discovered.4 Furthermore, recent studies show that mixed infections are common.2,5 In symptomatic patients, empirical amoebicidal therapy is warranted. However, to ensure that alternative diagnoses (eg, inflammatory bowel disease) that require different treatment are not overlooked, all attempts to accurately speciate Entamoeba complex should be undertaken. We acknowledge that speciation using the polymerase chain reaction is beyond the means of most laboratories, but this is not the case for enzyme immunoassay testing of stool samples, which is rapid, sensitive and relatively cheap. For asymptomatic patients who are carriers of E. histolytica cysts, the World Health Organization recommends treatment.5 However, in areas of low prevalence such as Australia, Entamoeba cysts are more likely to be non-pathogenic E. dispar or E. moshkovskii species than E. histolytica.3 Thus, in Australia, treatment would be unnecessary in a high proportion of patients. Furthermore, therapy requires a luminal agent (paramomycin), which is difficult to obtain. The most practical solution is to either give no treatment or to treat only those patients who have tested positive for E. histolytica.

Sebastiaan J van Hal · Damien J Stark · Debbie Marriott · Jock L Harkness

Clinical records Patient 1 A 55-year-old man presented with tenesmus, rectal bleeding and discharge of 3 weeks’ duration. He had a past history of treated syphilis and anal warts. High-resolution anoscopy, performed by a sexual health physician, revealed an extensive anterior ulcer distal to the dentate line, suggestive of anal carcinoma (Figure A). However, histological examination of repeated rectal biopsies revealed non-specific ulceration, with chronic inflammation in the adjacent rectal glandular mucosa. Patient 2 A 54-year-old man with previously treated syphilis presented with a 2-week history of per-rectal bleeding, pain and associated fevers. Colonoscopy, performed by a gastroenterologist, revealed extensive rectal ulceration. Histological examination of a biopsy from the ulcer revealed ulceration with mixed acute and chronic inflammatory cells and a lymphoid infiltrate, suggestive of a lymphoma (Figure B). A sigmoidoscopy was performed 7 days later, when the patient re-presented with worsening rectal pain and bleeding. Repeat rectal biopsies confirmed non-specific inflammation with atypical Epstein–Barr virus-associated lymphoid proliferation rather than lymphoma. Patient 3 A 43-year-old man with previous Kaposi’s sarcoma presented with a 2-month history of per-rectal bleeding and diarrhoea. Colonoscopy, performed by a surgeon, showed multiple rectal ulcers suggestive of Crohn’s disease (Figure C), but biopsies showed non-specific acute and chronic inflammatory infiltrates only. All three patients were HIV-infected men who have sex with men. They were receiving highly active antiretroviral therapy, with good virological control and CD4+ T cell counts. All were investigated for a broad range of diagnoses, including inflammatory bowel disease, colorectal malignancy, lymphoma and sexually transmitted infections; all underwent one or more invasive procedures by various specialists before being referred to our infectious diseases outpatient clinic between 2005 and 2006. After assessment at the clinic, the aetiology of the anorectal condition was determined in all cases by a simple rectal swab. The swab was initially tested for Chlamydia trachomatis using a routine nucleic acid amplification method. As these tests were initially positive, the samples were further analysed by sequencing of the outer membrane protein gene. This confirmed, in all three cases, that the strains were of the lymphogranuloma venereum (LGV) 2b serovar, which is commonly associated with LGV. Screening for other sexually transmitted infections was negative. All patients made a full clinical recovery after treatment with doxycycline 100 mg twice a day for 3 weeks. Patient 2 underwent a repeat colonoscopy 2 months later, which revealed complete resolution of the ulcer. Chlamydia trachomatis is a human pathogen and a common cause of sexually transmitted infections, including lymphogranuloma venereum (LGV).1 LGV was previously confined to endemic areas in tropical regions — principally Africa, India and northern South America. However, since 2003, LGV has emerged as an increasingly important infection worldwide, with outbreaks occurring in communities of men who have sex with men (MSM) in The Netherlands, Belgium, France, Germany, Sweden, the United Kingdom and North America.2-6 Risk factors identified in these outbreaks include HIV seropositivity, previously diagnosed sexually transmitted infections, concurrent ulcerative disease, and unprotected receptive anal sex with casual partners. In Australia, there have only been two previous reported cases of LGV. Both patients were MSM. One patient presented with inguinal lymphadenopathy acquired in Melbourne,7 while the other had anorectal LGV acquired after sexual exposure in Europe.8 Unlike other chlamydial infections, which are generally restricted to epithelial surfaces, LGV is invasive and causes severe inflammation, often with systemic symptoms and with a preference for lymphatic tissue.1 The manifestations of LGV infection vary depending on the site of inoculation, presenting either as a painful unilateral inguinal syndrome or an anorectal syndrome. Lessons from practice Lymphogranuloma venereum (LGV) is an invasive inflammatory disease of the urogenital tract caused by infection with Chlamydia trachomatis. LGV is an important cause of anorectal disease in men who have sex with men. Anorectal LGV may masquerade as inflammatory bowel disease, colorectal malignancy, lymphoma or other ulcerative rectal sexually transmitted infections. Diagnosis requires a high index of suspicion. It is important to take a detailed sexual history and conduct specific microbiological testing for C. trachomatis. Screening for coinfection, contact tracing, general education and health promotion are important public health components of managing LGV. LGV infection is characterised by three stages. In the first stage, the primary lesion is usually an asymptomatic small genital ulcer that heals spontaneously. This is followed by a painful inguinal lymphadenopathy associated with systemic features. Lymph node inflammation may progress to involve the surrounding subcutaneous tissue, causing an inflammatory mass (bubo) and/or abscess. Complications occur in 30% of cases as a result of bubo rupture and/or sinus tract or fistula formation. In anorectal disease, acute haemorrhagic inflammation of the colon and rectum is associated with involvement of perirectal lymphatic tissue.1,9 The third stage is characterised by chronic granulomatous inflammation leading to lymphatic obstruction, fibrosis and stricture formation.1 Clinical proctitis is a common problem in MSM, and C. trachomatis is one of the most frequent infectious agents found in this population. When suspected, C. trachomatis infections can be quickly identified and treated. However (as was the case with the patients described here), infected people may present to non-sexual-health practitioners (eg, gastroenterologists or colorectal surgeons) for persisting symptoms.9 Endoscopic features are non-specific, with a wide range of differential diagnoses including Crohn’s disease, lymphoma, anorectal carcinoma and other sexually transmitted ulcerative infections (eg, syphilis, herpes).3,4,9 Biopsies typically show only non-specific inflammatory features. C. trachomatis is divided into 15 serovars, labelled A, B, Ba, C–K and L1–L3, based on analysis of the major outer membrane protein. The various serovars are associated with specific disease manifestations: serovars A, B, Ba and C cause trachoma; serovars D–K are associated with urogenital infection; and serovars L1–L3 cause LGV.10 The L2 serovar can be further separated into L2, L2', L2a or L2b according to minor differences in their component amino acids.9 The commonly used commercial diagnostic tests for C. trachomatis are nucleic acid tests that can be performed on urine and on cervical and urethral swabs. Although not currently licensed for use on rectal swabs, the test may be used “off licence” and is the investigation of choice. Alternative tests, such as culture, are slow to perform and less sensitive, while serological tests cross-react with other Chlamydia species and can not distinguish between previous infection and current infection on single specimens. As commercial nucleic acid tests can not distinguish between uncomplicated rectal chlamydial infections (serovars D–K) and LGV (serovars L1–L3), directed testing is required (eg, outer-membrane protein sequencing). Therefore, to make a diagnosis of LGV, it is important at the outset to discuss the optimum specimen collection technique with a microbiologist at the laboratory to which the specimen will be sent. Two dry swabs should be sent with a specific request for LGV testing. This is a reference laboratory test and is offered by only a few public laboratories. The charge for the test is under the Medicare nucleic acid rebate, with no gap amount charged to the patient. The laboratory turnaround time for such a specimen is typically about 2 weeks from receipt. The correct diagnosis is essential, as treatment regimens recommended for LGV infection are much more prolonged than those for uncomplicated genital chlamydial infections — for example, a patient may receive 3 weeks’ treatment with doxcycline 100 mg twice a day or azithromycin 1 g weekly. However, good clinical trial data are lacking, and inadequate therapy may be associated with progressive disease and tissue destruction. Careful follow-up of the index patient is therefore essential. As with other sexually acquired infections, rigorous contact tracing is important to prevent further spread within the community. Counselling about healthy sexual practices is an important public health component of management, and patients should be alerted to the increased risk of HIV transmission associated with genital ulcer disease. A. Patient 1 — high-resolution anoscopy showing extensive ulceration distal to the dentate line. B. Patient 2 — biopsy from a rectal ulcer showing a lymphoid aggregate with a germinal centre (arrow) (haematoxylin and eosin stain; original magnification 3100). C. Patient 3 — colonoscopy showing multiple ulcerative lesions in the anorectal area.

Sebastiaan J van Hal MB ChB · Richard Hillman MD, FRCP · Damien J Stark BSc, PhD · Jock L Harkness FRCPA · Debbie Marriott FRACP, FRCPA

Measles is now rare in Australia, and cases can usually be linked to its importation from endemic countries. To prevent measles outbreaks in Australia, high vaccination coverage with two doses of vaccine must be sustained. All medical practitioners should consider a diagnosis of measles in a patient of any age who presents with fever and a non-vesiculating, non-itchy rash. If measles is suspected clinically, public health authorities should be immediately notified, so that testing and management of patients can be discussed and contact tracing initiated. When a patient is suspected of having measles, testing of a serum sample for measles-specific IgM and IgG antibodies should be requested urgently. Pathology laboratories should have effective protocols for immediately reporting positive measles-specific IgM antibody tests, or other results indicative of measles, to public health authorities.

David N Durrheim DrPH, MB ChB, FAFPHM · Heath Kelly MB BS, MPH, FAFPHM · Mark J Ferson MD, FRACP, FAFPHM · David Featherstone BSc

Infection control principles need to be at the core of Australian hospitals, not just an afterthought Methicillin-resistant Staphylococcus aureus (MRSA) infections continue to be an entrenched problem in hospitals throughout Australia,1-3 and create an added burden for hospital care, rather than simply replacing infections caused by more antibiotic-susceptible bacteria. The cost of not dealing with MRSA, as is currently the case in most Australian states, appears to be huge, including prolonged patient length of stay and reattendances to outpatient clinics, not to mention the suffering of affected patients. Yet many in the health sector feel overwhelmed by the MRSA problem, and see it as a part of life about which little can be done. We believe this is a faulty assumption — it is possible to make an impact. In some countries (eg, Denmark and the Netherlands), where “search and destroy” campaigns have been implemented, MRSA has been kept at very low levels in hospitals.4,5 In Western Australia, infections caused by multiresistant strains of MRSA in hospitals remain uncommon, partly due to screening and isolation of patients transferred from endemic areas, such as the eastern Australian states.6 In Brisbane, marked reductions of MRSA occurred when major hospitals were refurbished and more vigorous infection control programs introduced.3 In Victoria, significant reductions in hospital MRSA infections have been achieved by introducing better hand hygiene practices.2 We should not be surprised that bacteria such as S. aureus have learned to adapt and survive in the antibiotic-rich environment of a modern hospital. Ultimately, we cannot avoid the Darwinian principle of natural selection and thus will always need new antibiotics. However, we also need to consider another unavoidable principle, not from evolution, but from history: when you crowd sick or stressed people together, epidemics are likely to emerge. Military history is replete with examples of disease outbreaks in the crowded ranks causing more damage than the enemy itself. Australia is “at peace”, yet we have overcrowded emergency departments, where rows of casualties wait endlessly for a bed in the completely full hospital — making our hospitals resemble war zones! This crowding results in worse outcomes for patients.7 How many Australian health care workers and students, all with varying goals and agendas, understand and practise infection control principles well enough to protect their patients from cross-infection? What about the patient’s agenda — getting better and getting home without a hospital-inflicted wound or complication? Clearly, we who work in hospitals can and should improve our act. However, regardless of how much we improve our personal infection control practices, there is still an irreducible philosophical tension between an economist’s model and an ideal hospital. Our current hospital system seems to be run predominantly with reference to economic outcome measures — more and more throughput, same staff numbers, but with older and sicker patients. We need hospitals to be built and managed so that infection control is their main priority. Somewhere between our current reality and the dream of infectious diseases physicians, a new balance needs to be reached. What do we need to do?We already have numerous guidelines — we need to follow them. Recently, the “Protecting 5 million lives from harm” campaign again highlighted many of the crucial issues.8 Leadership is needed, in hospitals and at the state and national levels. We need basic infection control practices to be followed by all clinical staff and students — in particular, hand hygiene. We can’t continue to accept that a good result is when 50% of staff comply. Enough equipment and supplies (eg, gloves, gowns) must always be available so that health care workers can comply easily. These workers also need backup, with adequate personnel in infection control, microbiology and environmental services. The basic components of any infection control campaign are: Hand hygiene — use of an alcohol-based hand rub, soap and water, and gloves; Decontamination of the environment and shared equipment; Contact precautions for infected and colonised patients; Active surveillance and screening; Effective programs that prevent common infections (eg, intravascular catheter sepsis, surgical site infections); Good antibiotic stewardship; and Better hospital design to include more single rooms for patients. To make these components work, we need staff in our hospitals to accept that MRSA causes needless morbidity and mortality, and to aim for a near-zero infection rate for health care-acquired infections. We need to accept that health care workers are key conduits for spreading MRSA. Staff can then make a major contribution to stopping its spread by adhering to basic infection control practices. Hospital managers and health departments are equally responsible for ensuring that people can do their jobs under reasonable working conditions. We need to recognise that MRSA is a signal that the system is stressed. We need to measure our successes and failures.9 Is it a coincidence that the state with the lowest prevalence of health care-associated MRSA (Western Australia) is also the only state in which MRSA infections are notifiable? We need better hospital design so that contact precautions and single-room isolation can be achieved. This means we need to insist, as is now recommended in many countries, that all new hospitals have nearly all patient accommodation as either single rooms or shared rooms with a maximum of two patients. Otherwise, how can adequate spatial separation of MRSA-colonised or infected patients be ensured? MRSA remains a scourge. Programs that effectively reduce the rate of MRSA infections in hospitals are well known, and some have been successfully implemented in Australia. For these to be effective, however, requires a culture change in the attitude of most Australian health care workers and a new era of government leadership in providing adequately resourced modern hospital facilities with infection control principles at the core of their design, not just added as an afterthought. A better understanding of MRSA and basic infection control issues is needed by the entire community (taxpayers, architects, engineers, health care workers, students, governments, administrators, and patients) if we are to ever finally control MRSA and other health care-associated pathogens.

Peter J Collignon FASM, FRCPA, FRACP · M Lindsay Grayson MD, FRACP, FAFPHM · Paul D R Johnson MB BS, PhD, FRACP

Many lower respiratory tract infections (LRTIs) are caused by organisms that do not require antibiotics or could be safely treated with narrow-spectrum antibiotics. Reducing the unnecessary use of antibiotics, particularly broad-spectrum agents, could reduce costs and side effects and delay the emergence of antibiotic-resistant organisms. Various point-of-care tests are becoming available to help clinicians identify the cause of LRTIs at the time of consultation. Point-of-care tests can be used to diagnose influenza, pneumococcal infections, Legionella and respiratory syncytial virus infections, thus allowing early decisions to be made on appropriate management.

Patrick G P Charles MB BS, FRACP · M Lindsay Grayson FRACP, MD, FAFPHM

Point-of-care tests (POCTs) are available for rapid, “bedside” diagnosis of some causes of community-acquired pneumonia. POCTs complement other laboratory investigations for pneumonia. Although their sensitivity and specificity are improving, they are generally less sensitive than nucleic acid amplification and culture techniques. Questions remain as to the most cost-effective use of POCTs in clinical practice. To ensure their maximum value for both individual patients and the public health system, POCTs are probably best used as part of laboratory-designed algorithms for investigating pneumonia. POCTs are a valuable tool for surveillance, for rapid investigation of outbreaks, and for use in laboratories with limited diagnostic facilities.

Dominic E Dwyer MD, FRACP, FRCPA · Vitali Sintchenko MB BS, PhD, FRCPA

To the Editor: Human normal immunoglobulin (NIG) has historically been used to provide passive immunity against hepatitis A infection for susceptible travellers to areas where the virus is endemic.1 The introduction of effective hepatitis A vaccines in recent years (which result in active, long-term immunity to the virus) should have largely replaced the use of NIG for travel prophylaxis.2 However, the Australian Red Cross Blood Service still receives requests to supply NIG for travellers, even though the intended recipients have no contraindications to vaccination. Requests for use of NIG for this purpose appear in many cases to be a consequence of the “out-of-pocket” cost to the patient of the hepatitis A vaccine, which is about $70–$100 (depending on the formulation used and the private dispensing fee charged). In contrast, NIG is provided free of charge to the recipient, but the community still incurs substantial costs related to blood collection and fractionation of plasma products. There is also the concern of unnecessary exposure of a healthy traveller to a pooled plasma product, which, despite blood donor screening, dedicated viral inactivation steps, and an excellent safety record in Australia, may theoretically transmit infectious agents. In addition, even if a small amount of NIG is used for this purpose, the plasma source would be better used for production of greater amounts of other scarce plasma-derived products (such as intravenous immunoglobulin). While NIG can effectively prevent hepatitis A infection from developing in susceptible contacts, immunity is short-lived and likely to be inferior to the results of active vaccination.1-3 Accordingly, NIG is only indicated for at-risk people who have a contraindication to vaccination, or in whom there is insufficient time to mount an endogenous antibody response (active immunity develops within 7–10 days of vaccination,3 and vaccination may also prevent hepatitis A infection even when the vaccine has been administered up to a week after exposure4). Use of NIG is also appropriate where at-risk contacts may be unable to mount a protective antibody response because they have a congenital or acquired immune deficiency. Although the extent of NIG use for travellers appears to be limited, we wish to highlight that, in the absence of contraindications to vaccination, it can no longer be advocated as best practice, and it is certainly not an appropriate cost-saving measure.

Jake Shortt · Denis Spelman · Erica M Wood

To the Editor: Rabies vaccine is recommended for pre-exposure prophylaxis in travellers over 1 year old who intend to travel to predominantly developing countries where canine rabies is endemic. The incidence of dog bites in such countries is relatively high, being more common among travellers than typhoid fever.1 Postexposure rabies treatment of pre-immunised travellers is simpler, cheaper and safer than treatment of those who have not been immunised. Rabies vaccines currently available in Australia are given intramuscularly as three doses of 1.0 mL on Days 0, 7, and 21–28, but are relatively expensive at more than $100 per dose. Some travellers will choose not to be vaccinated because of this cost. For at-risk travellers who might choose to decline vaccination because of the cost, and to facilitate use of pre-exposure vaccination in poorer countries, the World Health Organization approves the intradermal route of vaccination, where 0.1 mL of vaccine is administered, also on Days 0, 7 and 21–28.2 However, the intradermal technique is technically more difficult, may result in lower antibody levels that decline more quickly, and may be interfered with by concurrent administration of chloroquine or immunosuppressants. The Australian immunisation handbook therefore recommends that this technique be performed by vaccinators experienced in the technique, and that satisfactory antibody production is confirmed after vaccination.3 Antibody levels of at least 0.5 IU/mL are considered protective, and the commercial enzyme immunoassay, available under Medicare, has been shown to correlate well with the gold-standard virus neutralisation test.4 We have been using the intradermal method for over 10 years for travellers considered at high risk, but who decline vaccine on cost alone; we use imported human diploid cell vaccine of potency of at least 2.5 IU/mL. As several travellers can be vaccinated from the same vial, costs are $30–$40 per dose, and vials can be stored and reused within 7 days under aseptic conditions. However, travellers must be vaccinated 7–8 weeks before departure to enable antibody testing and a booster vaccination if required. Recent analysis of 1532 non-immunosuppressed travellers (aged between 9 and 77 years; 55% female) who received three intradermal doses of 0.1 mL rabies vaccine on Days 0, 7, and 21–28 in our Melbourne clinic showed that only seven (0.46%) failed to reach the protective antibody level of 0.5 IU/mL on testing 2–4 weeks after the third dose, with readings of 0.4 IU/mL (in four), 0.3 IU/mL (in two) and 0.2 IU/mL (in one). None had undetectable antibody levels. All seven were advised to receive an intramuscular booster dose of 1.0 mL. These data support the contention that the intradermal method is appropriate for use in travellers who may otherwise decline pre-exposure rabies vaccination, when the vaccine is administered by vaccinators with relevant experience.5 Recipients of intradermal rabies vaccine who have satisfactory antibody levels may be considered fully vaccinated in the postexposure situation and managed accordingly.

Anthony Gherardin · Sonny Lau

To the editor: Bairnsdale ulcer is known by the eponyms Buruli in Uganda, Kakerifu in Zaire, Kumusi in New Guinea, and was formerly referred to as Searls’ ulcer in Australia. In the original 1948 article describing the causative organism,1 MacCallum and colleagues acknowledged assistance from Drs Alsop, Clay and Searls, in that (alphabetical) order. In sending material to Melbourne for examination, these doctors of the Bairnsdale Clinic described the ulcers, and also commented on the similarity of their appearance in the first three patients. J R Searls, after whom the ulcer was originally named, was regarded as an excellent general practitioner. He died in 1971.

Derek H Meyers