Volume 188 Issue 3

Australia, like other high-income countries with a low TB incidence, faces special challenges in controlling TB Books with optimistic titles such as Triumph over tuberculosis, The retreat of tuberculosis and The miracle of empty beds were published in the 1970s and 1980s. Readers of the Journal may therefore be surprised to find six articles on tuberculosis (TB) in this one issue in 2008.1-6 Far from having dis-appeared, TB is the dis-ease that still affects the dis-placed, the dis-advantaged, the dis-possessed, the dis-rupted and those with dis-abled immune systems. Displaced persons and migrants accounted for 85.5% of the 1201 TB cases in Australia in 2006.7 Overseas-born TB patients commonly come from India, Vietnam, Indonesia, China and the Philippines. Sudan and Somalia have more recently joined this list, following the shift in Australia’s immigration policy to accept more African refugees. These national figures are reflected in the letter from Robinson et al, which describes a retrospective review of TB cases seen at The Children’s Hospital at Westmead, Sydney, between 2004 and 2006 (&rarr Tuberculosis in children: a tertiary centre perspective).5 Of the 23 children with active TB disease, 18 (73%) were born overseas, mainly in Africa and the Indian subcontinent. Compared with data from 1982–1991, the proportion and number of latent TB infections diagnosed in children had increased due to active screening of refugee populations. The article by Dobler et al highlights the successful outcome of directly observed treatment for TB cases in Australia, while alerting Australian doctors to the fact that migrants with treated TB who visit their TB-endemic country of birth may develop a second episode of TB that represents a new infection rather than a relapse of their previous disease (→ Recurrence of tuberculosis at a Sydney chest clinic between 1994 and 2006: reactivation or reinfection?).1 TB also affects the disadvantaged and dispossessed, as illustrated by the fact that the TB incidence in Australia’s Indigenous population has been 7–15 times higher than in the non-Indigenous Australian-born population over the past decade.7 TB affects those with disabled immune systems. People infected with HIV have nearly 10 times the lifetime risk of developing TB compared with HIV-negative people.8 HIV/TB coinfection is not considered a major problem in Australia, with only 11 HIV/TB patients identified in 2006.7 However, the national TB notification system recorded the HIV status of only 35.2% of TB patients in 2006.7 Emerson and Post rightly exhort Australian clinicians to offer HIV testing to all TB patients (→ To routinely offer testing for HIV infection in all cases of tuberculosis: a rational clinical approach?).2 In fact, establishing the HIV status of TB patients could be regarded as an expected standard of care. Other immunocompromising conditions — such as chronic renal failure, transplantation, or treatment with glucocorticoids or tumour necrosis factor α inhibitors — also increase the risk of TB reactivation twofold or more.8 For patients about to receive tumour necrosis factor α inhibitor therapy, Gupta et al propose a screening strategy for latent TB infection using an interferon γ release assay, such as QuantiFERON-TB Gold (Cellestis, Melbourne, Vic) or T-SPOT. TB (Oxford Immunotec, Oxford, UK) (→ Tumour necrosis factor α inhibitors: screening for tuberculosis infection in inflammatory bowel disease).6 The optimal application and interpretation of these assays is controversial. For example, although various versions of the QuantiFERON assay have been approved by the United States Food and Drug Administration and endorsed by the US Centers for Disease Control and Prevention, Australian and Canadian TB authorities are continuing to recommend the tuberculin skin test for diagnosing latent TB infections in most patient groups until the sensitivity, specificity and cost-effectiveness of interferon γ release assays have been better defined.9,10 Finally, like many other infectious diseases, TB affects populations that are disrupted or disorganised due to socioeconomic upheavals, rapid urbanisation, persistent poverty, conflict or war, and where public health systems are therefore either weak or non-existent.11 In a speech to the Lowy Institute in July 2007, Kevin Rudd (then Federal Opposition Leader) highlighted the “arc of instability” to Australia’s near north, noting the recent political unrest in East Timor and several Pacific Island countries and the continuing impoverishment in parts of Indonesia.12 The link between TB and this arc of instability is amply demonstrated by the articles in this issue about illegal foreign fishermen with TB (→ Tuberculosis in illegal foreign fishermen: whose public health are we protecting?)4 and people with multidrug-resistant TB from Papua New Guinea seeking medical care in the “Torres Strait Protected Zone” (→ Evidence of primary transmission of multidrug-resistant tuberculosis in the Western Province of Papua New Guinea).3 For example, Gray et al4 estimated the prevalence of all TB diagnoses among illegal fishermen screened in Darwin over a 15-month period to be 1360 cases per 100 000 population! How should Australia respond internally to this persisting TB problem? Limiting migration and ostracising migrants is not indicated, acceptable or practicable in the “global village” of the 21st century. We require migrants and temporary visitors for our economy, for plugging skill gaps in our workforce, and for nation building. Moreover, molecular epidemiological studies in Australia and overseas have demonstrated that there is negligible transmission of TB from migrant communities to the general population.13,14 The appropriate interventions are to optimise pre- and post-migration detection of active TB disease, to familiarise migrants with the TB clinical services that are freely available if they develop disease, and to detect and treat latent TB infections among subgroups of migrants who would benefit from this intervention (eg, children under 15 years old). The 2006 annual report of the National Tuberculosis Advisory Committee does highlight one migrant subgroup requiring particular attention by documenting that the number of TB cases among health care workers (HCWs) has risen from 34 in 2001 to 65 in 2006.7 This rise is attributable to the increasing recruitment of HCWs from high-incidence TB countries. There were no reports of TB transmission from HCWs to patients in 2006.7 Nonetheless, public and private health institutions, particularly those recruiting HCWs from high-incidence TB countries, must ensure that adequate TB screening is undertaken before and during employment. In common with other high-income countries with a low TB incidence, Australia faces special challenges in controlling TB.15 Continuing undergraduate and postgraduate education of medical and nursing personnel is required to ensure that health professionals remember to “think TB” in at-risk patients. Despite the low incidence of TB, federal and state governments must be encouraged to continue funding TB control efforts and must be dissuaded from devolving TB care from specialised TB services to general clinics in city hospitals. The closure of specialised TB services contributed to the TB epidemic in New York City in the 1980s and 1990s, which may ultimately have cost several billion dollars to control.16 The low incidence of TB may also discourage pharmaceutical companies from selling small volumes of anti-TB drugs at narrow profit margins in Australia, which is a geographically isolated market with stringent regulatory requirements. Federal administrators may need to develop novel solutions to ensure reliable anti-TB drug supplies into the future. How should Australia respond externally to the persisting problem of TB? As long ago as 1993, the TB problem was declared a global emergency requiring a global response. Rudd’s 2007 speech to the Lowy Institute proposed a new strategic partnership with our northern neighbours that emphasised proactive socioeconomic development and promised an increase in Australia’s official development assistance (as a percentage of gross national income).12 TB is one issue for which this rhetoric should become action. In responding to TB as a global emergency, Australia needs to provide direct continuing TB care in specific circumstances to foreign nationals, such as people with multidrug-resistant TB entering the “Torres Strait Protected Zone” and illegal fishermen entering Australian waters.3,4 Addressing only “acute life-threatening conditions” in these groups, as quoted in the article by Gilpin and colleagues,3 is short-sighted in view of the fact that TB is both communicable and potentially deadly. A collaborative approach is necessary in Australia’s border areas. More generally, Australia’s clinical and laboratory expertise in TB control could be harnessed to assist with national TB programs in neighbouring countries through properly funded bilateral partnerships. Such collaboration would be to our mutual benefit. Investment in TB programs in neighbouring high-incidence countries is one control strategy that has been largely ignored by high-income countries with low TB incidence. One analysis suggested that US-funded expansion of TB care into Mexico, Haiti and the Dominican Republic could reduce TB disease among migrants from these countries and would produce net savings for the US.17 The authors suggested that their findings could be generalised to other developed countries with large migrant intakes and should encourage those countries to fund TB control efforts abroad. TB really is where philanthropy and self-interest meet!

Ivan Bastian MB BS, PhD, FRCPA · Vicki L Krause MD, DTM

The need for stimulant treatment must be assessed regularly In a United States legal action in 2000 about educational neglect, Albany County judge G E Maney ordered the parents to resume administering methylphenidate to 7-year-old Kyle Carroll.1 At the time, this controversial ruling was understandable, because controlled trials of stimulant treatment (dexamphetamine and methylphenidate) for attention deficit hyperactivity disorder (ADHD) had consistently shown that stimulants reduce ADHD symptoms. The catch is that trials have examined short-term effectiveness (usually over less than 6 months), while ADHD is a chronic condition. In 1992, the US National Institute of Mental Health funded the Multimodal Treatment Study of Children with ADHD (MTA) to examine the long-term effects of routine community management versus carefully delivered treatments. Children with ADHD, combined type (that is, showing symptoms of inattention, impulsivity and hyperactivity), were randomly allocated to medication, psychosocial treatment, a combination of both, or standard community care. The medication group received treatment with methylphenidate in which an optimal dose was titrated, with blinding, to achieve maximum benefit. The psychosocial group received a variety of interventions that consisted of parent training, a summer treatment camp and classroom management. Those in the routine care group were given information about services and left to their own devices. In total, 579 children with a mean age of 8.5 years were randomly allocated to the four groups, about 145 in each. After 14 months, children in both the medication groups showed greater improvement than those in the behavioural treatment and community care groups, leading the authors to conclude that “carefully crafted medication management was superior to the behavioral treatment and to routine clinical care that included medication”.2 The results were influential in treatment guidelines3 and clinical practice. Participants were naturalistically followed up 1 and 2 years after the end of the trial. The results of the last follow-up (3 years from the onset of treatment), of 84% of the original sample of children (then aged 10–13 years), showed that none of the treatment groups differed on any of the five clinical and functional outcomes (parent- and teacher-rated ADHD and oppositional symptoms, reading achievement scores, social skills, and functional impairment).4 Also, there were no differences in substance use or delinquency, with the exception of a slightly lower rate of substance use among those in the psychosocial treatment group.5 While improvement had been steepest during the first 14 months (mostly in the methylphenidate group), this levelled off, and at 3 years, all groups showed a similar improvement; the methylphenidate group had not deteriorated but the other groups had caught up.4 Speculation is bound to follow these results, which have many ambiguities and nuances. For example, this follow-up was not part of the controlled trial and, as happens in practice, children switched on and off their medication over time in the various groups, with consequent difficulties for analysis and interpretation. The results highlight several issues. First, it suggests the Rolls-Royce model (medication plus psychosocial treatment involving the child, family, and school) is not more effective in the long run than any of the other treatments, including the often maligned community care. The combined treatment is seen as the ideal, but is rarely delivered in practice, because of high cost and the burden for parents and schools.6 Second, there seems to be a “growing out of” or developmental factor at work. Epidemiological7 and follow-up8 data have consistently reported a reduction in ADHD symptoms with increasing age — although some individuals continue to show problems. This is also consistent with findings that brains of children with ADHD, rather than developing abnormally (as in autism), mature later.9 The MTA did not include a placebo group, which might have led to the conclusion that regression to the mean or maturation itself were the reasons for improvement. If that was the case, it is possible that helping families and schools contain children’s ADHD behaviour during the middle and late primary school years with minimal interventions (eg, parent management training) may be enough for a proportion — but not all — of these children to get better, or for medication to be required mostly during this developmental period. Finally, the MTA confirmed that medication can cause retardation of growth, including weight, particularly during the first year of treatment.10 While results of one study rarely justify drastic changes of practice, the findings underscore the complexity of ADHD, show that stimulant drugs are far from being a silver bullet, and that there is much that we do not yet know. This does not mean that stimulants no longer have a place in the treatment of ADHD. However, that place has shrunk, and clinicians should be circumspect when assessing the need for ongoing treatment (eg, through medication breaks). Much needs to be done to clarify who benefits the most from medication, at what developmental point stimulants are most useful, and for how long they should be taken. It is also not known whether these results apply to the slow-release formulations (which may enhance adherence) and to atomoxetine (a non-stimulant drug with antidepressant activity, which is thought to act by inhibition of the presynaptic noradrenalin transporter). Parents, often caught in the bind of concerns about their children taking medication and fear of the consequences of not treating them, might be comforted by these findings. One wonders whether Judge Maney would have issued the same order to Kyle Carroll’s parents had he been aware of this information.

Joseph M Rey MB BS, PhD, FRANZCP

Objective: To evaluate and compare the clinical outcomes of children with cystic fibrosis (CF) managed primarily at a tertiary cystic fibrosis centre (CFC) with those treated at regional centres by local health care professionals and the cystic fibrosis outreach service (CFOS).Design, setting and patients: Retrospective study of 273 children with CF born between 19 October 1982 and 19 February 2002 and with clinical data available between 1 January 2000 and 31 December 2002. Patients were grouped into CFC (n = 131) or CFOS (n = 142), with CFOS then further categorised into three groups depending on the level of care they received.Main outcome measures: Pulmonary function, Pseudomonas aeruginosa status, height and weight z scores, and hospital admission rates.Results: There were no significant differences in pulmonary function, P. aeruginosa status, or height and weight z scores between children managed by CFC or by CFOS. Children receiving more care at the CFC (level of care [LOC] 1 and 2) were more likely to have multiple hospital admissions than children receiving more care in regional areas (LOC 3 and 4) (P < 0.001).Conclusion: The CFOS model provides effective delivery of specialised multidisciplinary care to children and adolescents living in rural and regional Queensland.

Clare L Thomas MB BS, FRACP · Peter K O’Rourke BSc, BA, PhD · Claire E Wainwright MB BS, MD

Objective: To describe the incidence and risk of suicide in cancer patients in Western Australia from 1981 to 2002.Design, setting and patients: Retrospective cohort study of patients diagnosed with cancer in WA from 1981 to 2002, using data from the WA Linked Database.Main outcome measure: Age-standardised mortality ratios (SMRs).Results: A total of 121 533 patients were diagnosed with cancer, corresponding to a total of 543 696 person-years at risk. There were 129 suicides in this group (108 in men). The SMR for suicide in cancer patients was 1.61 (95% CI, 1.36–1.92). An initial period of peak risk was seen in the first 3 months after cancer diagnosis (SMR, 5.75; 95% CI, 3.89–8.51), mainly in patients with a poor prognosis. A second peak period of risk was found to occur 12–14 months after diagnosis (SMR, 2.33; 95% CI, 1.11–4.89) in those with a good or moderate prognosis.Conclusion: The rate of suicide in cancer patients in WA is low and represents an excess of two to three suicides per year, or 0.3% of all cancer deaths, comparable to studies in other Western countries. The risk is highest in the first 3 months after diagnosis, and a second period of increased risk 12–14 months after diagnosis may occur in response to cancer recurrence or treatment failure.

Nigel R C Dormer MB BS, MRCGP, DRCOG · Kieran A McCaul MPH · Linda J Kristjanson RN, BN, PhD

Objective: To document demographic details, prevalence of tuberculosis (TB), and completion of TB treatment in illegal foreign fishermen detained in Australia.Design and participants: Clinical audit of 1471 illegal foreign fishermen who underwent health assessments in Darwin between 28 September 2005 and 31 December 2006.Main outcome measures: Demographic details, diagnoses of smear-positive and culture-positive TB, drug sensitivity results and treatment completion.Results: 1471 illegal fishermen underwent health assessments, including chest x-ray screening. All were male and 93.8% were from Indonesia. Of the 31 fishermen (2.1%) admitted to hospital with chest x-rays suggestive of TB, 20 were diagnosed with TB (15 culture-proven; 5 according to clinical and radiological criteria) and 18 commenced treatment. There were 8 smear-positive cases and one multidrug-resistant TB case. The prevalence of culture-positive TB was very high at 1020 per 100 000 patients. All fishermen were deported before treatment completion, and all were lost to follow-up.Conclusions: The health assessment process successfully detected cases of TB in illegal foreign fishermen, enabling treatment to commence and the local public’s health to be protected. Treatment completion in illegal foreign fishermen may be as low as zero; deporting fishermen before curative treatment is completed undermines TB control efforts and may lead to an emergence of drug resistance and an increased burden of active TB disease in our region.

Natalie J Gray MB BS(Hons), MIPH(Hons), BSc/LLB(Hons) · Meredith Hansen-Knarhoi RN, RM, DipTropNsg, MPH · Vicki L Krause MD, DTM

Objective: To review patient outcomes and the molecular epidemiology of multidrug-resistant tuberculosis (MDR-TB) strains isolated from patients living in the Western Province of Papua New Guinea (PNG) seeking treatment in Australia.Design, setting and participants: Review of all cases of MDR-TB among people living in the open border region between the Western Province of PNG and the Torres Strait Islands of Australia who presented to health clinics in the region between 2000 and 2006. All cases of suspected TB were bacteriologically confirmed at the time of presentation by the Mycobacterium Reference Laboratory in Brisbane.Main outcome measures: Drug resistance patterns; drug use and duration; molecular typing of TB strains; patient outcomes.Results: Between 2000 and 2006, 60 patients from the Western Province of PNG were diagnosed with TB, of which 15 had MDR-TB. Mortality was high, although no patient who was able to maintain access to supervised therapy died. All 15 MDR-TB isolates were Beijing-family strains showing the same unique mycobacterial interspersed repetitive unit (MIRU) profile, with the exception of a single strain that differed by a single repeat at one locus. Restriction fragment length polymorphism (RFLP) typing on 10 of these strains further differentiated them into two distinct clusters.Conclusion: Transmission of MDR-TB is occurring in the Western Province of PNG. Additional resources are urgently needed to interrupt the ongoing transmission of MDR-TB from the Western Province of PNG to the Torres Strait Islands. Good supervision and management of patient treatment, which includes ensuring a regular supply of second-line anti-TB drugs, are essential elements of TB control.

Christopher M Gilpin PhD, MPH · Graham Simpson MD, FRACP · Stephen Vincent MB BS(Hons), FRACP · Terry P O’Brien RN · Trevor A Knight RN · Maria Globan BSc · Christopher Coulter FRACP, FRCPA · Anastasios Konstantinos MB BS, MPH

Objective: To estimate the incidence of recurrence of culture-positive tuberculosis (TB) and the relative contributions of reinfection and reactivation (based on DNA fingerprinting).Design, setting and participants: Retrospective analysis of all culture-positive TB notifications between 1994 and 2006 from Liverpool Chest Clinic in the south-west of Sydney. Patients with more than one notification of culture-positive TB during this period were identified. Genotyping of Mycobacterium tuberculosis was used to determine whether recurrence was due to reinfection or reactivation.Main outcome measures: Estimation of the incidence of recurrence of culture-positive TB (cases per 100 000 person-years of follow-up), and the proportions of reinfection and reactivation.Results: Three cases of recurrent culture-positive disease were identified (incidence of recurrence: 57.7 per 100 000 person-years of follow-up). All three patients were treated with directly observed therapy. Two of these patients had evidence of reinfection with different strains; both were natives of a country with a high incidence of TB and had returned to that country after the initial episode. The other patient had evidence of reactivation of the initial strain, indicating secondary failure of treatment. This patient had poor adherence to treatment.Conclusions: Our observations suggest there is a very low rate of reactivation of tuberculosis. The low incidence of recurrence due to reinfection reflects the low incidence of tuberculosis in Australia. When reinfection does occur, this probably has been sustained during residence in a country with a high incidence of tuberculosis.

Claudia C Dobler MB BS, MD · Guy B Marks MB BS, PhD, FRACP · Sheila E Simpson RN, MPH · A B Hamish Crawford MB ChB, FRACP

Five cases of methaemoglobinaemia after ingestion of sodium nitrite occurred in two clusters in Sydney in 2006. All cases were unintentional poisonings following use in cooking of an imported compound sold as a food additive. In all cases, methaemoglobinaemia was recognised early and treated promptly, with all patients making a full recovery. These cases highlight the importance of accurate food labelling and surveillance of imported goods. Clinical recordIn 2006, at Liverpool Hospital in Sydney, two separate clusters of patients presented to the emergency department with cyanosis after consuming home-prepared food to which sodium nitrite had been added. In the first cluster, a husband and wife of Vietnamese–Chinese origin developed cyanosis and dyspnoea after consuming homemade rice cakes containing “Nutre Powder” and “Borax Powder”, which were commonly available from local Asian food stores in the area. Both patients arrived by ambulance and, despite oxygen therapy, remained cyanotic. Their blood samples had a distinctive chocolate brown appearance, and laboratory testing confirmed methaemoglobinaemia. The husband, who was the more unwell, had a measured methaemoglobin level of 57%. After treatment with intravenous methylene blue, his condition rapidly improved. The wife, who had a methaemoglobin level of 21%, was treated supportively with oxygen and monitored closely. Both patients were admitted to the intensive care unit for a brief period of observation before being transferred to the haematology unit. Their subsequent progress was uneventful, and both patients were discharged from hospital 2 days later. On request from medical staff, the couple brought into the hospital the two packets used, both containing whitish powder. The first was labelled “Goldfish” brand “Borax” and the second, “Goldfish” brand “Nutre Powder” (Box). No further information about the contents was printed on the packaging. The packets were imported through a specialty Asian food distributor based in Melbourne, and the wife claimed they were commonly available food additives. She had used both ingredients in the meal she prepared that evening from a recipe given to her by her mother. She also claimed her mother had previously used the products in China without incident. Neither patient knew the composition of the products, and questioning of the product’s importer by the medical team yielded no further information. Two weeks later, a second cluster of three new cases, involving a Vietnamese family unrelated to the index cases, presented to Liverpool Hospital emergency department with identical symptoms after eating a pork dish prepared using an unidentified white powder. Laboratory testing again confirmed methaemoglobinaemia, with levels ranging from 39% to 51%. Intravenous methylene blue was administered, leading to rapid clinical improvement. All three patients made uneventful recoveries after being observed in the emergency department overnight and were released from hospital the next day. In both clusters, the onset of initial symptoms, such as vomiting, shortness of breath and dizziness, was dramatic, within minutes of consuming the contaminated food preparations. In the second cluster, two family members who had eaten the contaminated pork dish noticed the symptoms just after leaving home. They called back to warn the others that the food might be contaminated, but the others had already consumed the dish as well. A fourth person in that cluster also became ill, but had much less severe symptoms, having eaten only a small amount. She was seen by paramedics but not transported to hospital with the others. On review by her local doctor the next day, she had made a full recovery. Investigation by the New South Wales Food Authority and staff of the Public Health Unit of Sydney South West Area Health Service found that identical Goldfish brand Nutre Powder had been used in food consumed by the patients in the second cluster, reportedly as a flavour enhancer. The packages were purchased from separate local retailers. Importantly, this group was found not to have been exposed to any other known causes of methaemoglobinaemia. Residual Nutre Powder from both clusters and Borax Powder from the first cluster were submitted to the Division of Analytical Laboratories in Lidcombe, Sydney, for testing. Those labelled Nutre Powder contained 100% sodium nitrite, while the packet labelled Borax contained 100% sodium tetraborate. On the day that laboratory results on the additives used by the first cluster patients became available, NSW Health alerted hospital emergency departments and the public to the risk of methaemoglobinaemia associated with ingestion of Nutre Powder. As Goldfish brand Nutre Powder was imported via Victoria, the Victorian Department of Human Services initiated a national recall after the discovery of nutritional information on some packets of the products, implying that they were intended for human consumption. The Borax packets and two other packets labelled “Natural Powder” and “Natural Baking Powder”, which were also found to contain sodium nitrite, were recalled as well. Nevertheless, packets labelled Nutre Powder were found for sale in Asian grocery stores in NSW several months after the national recall, and the proprietors denied any knowledge about the product being potentially harmful or illegal for sale as a food additive. They were directed to the NSW Food Authority and have since stopped selling these products. DiscussionMethaemoglobinaemia is a potentially fatal condition in which native haemoglobin loses its ability to carry oxygen due to oxidation of the ferrous iron component of the haem molecule to the ferric state. Ferric forms of the haem molecule are unable to bind oxygen, and the oxygen affinity of accompanying ferrous haems in the haemoglobin tetramer is increased. As a result, the oxygen dissociation curve is “left shifted”, and oxygen delivery to the tissues is impaired.1 Ferric forms of the haem molecule are generated physiologically by deoxygenation, but are kept at low levels by endogenous haemoglobin reduction mechanisms, so that blood concentrations of methaemoglobin do not normally exceed 1%–2%.2 Hereditary causes of methaemoglobinaemia are well described but rare.3 Most reported cases arise from exposure to an oxidising agent, including those containing nitrites. Symptoms include nausea, vomiting, lethargy, shortness of breath, obtundation and coma. Patients typically present with profound cyanosis and have a deeply greyish-blue appearance. Blood samples from affected individuals often have a characteristic chocolate brown colour. The degree of oxygen desaturation varies with the degree of methaemoglobinaemia, but may not correlate well clinically and therefore is not necessarily a reliable predictor of outcome. Pulse oximetry readings of oxygen saturation are generally inaccurate, and arterial blood gas measurements frequently show normal dissolved oxygen and carbon dioxide tensions with falsely elevated oxygen saturations.4 The observed cyanosis is refractory to standard oxygen therapy. Despite this, management of methaemoglobinaemia comprises both supportive measures, such as oxygen therapy, and intravenous methylene blue administration in moderate to severe cases. Methylene blue is reduced by the action of a normally minor enzyme pathway involving reduced nicotinamide adenine dinucleotide phosphate (NADPH) — methaemoglobin reductase. The reduced form of methylene blue, leukomethylene blue, can then go on to reduce methaemoglobin to haemoglobin.5,6 Methylene blue (2 mg/kg bodyweight as a 1% solution) is administered to patients with methaemoglobin levels exceeding 25%–30% and to patients with underlying anaemia or cardiac or respiratory disease, in whom tissue oxygen delivery might already be impaired. While methylene blue is generally well tolerated, it must be administered with caution to people with severe renal impairment and is relatively contraindicated in those with glucose-6-phosphate dehydrogenase (G6PD) deficiency, as it may lead to profound oxidative haemolysis in these individuals without lowering methaemoglobin levels, and, indeed, has been reported to cause methaemoglobinaemia itself.7 Of interest, follow-up of one of the patients who was given methylene blue demonstrated G6PD deficiency, although no adverse effects were seen clinically. G6PD deficiency is more common in South-East Asian populations, where it is believed to offer some protection against malaria.8 Thus, although an effective antidote for nitrite-induced methaemoglobinaemia exists, it is not without risk, which can present a management dilemma in an emergency setting where rapid assessment for G6PD deficiency is not available. Rapid administration of methylene blue has also been associated with local pain and tissue necrosis.9 While sodium tetraborate is used as a food additive in some countries — particularly in noodles, where it is believed to improve colour, texture and flavour — this use is prohibited in Australia. Though potentially fatal in large doses, it is not known to cause methaemoglobinaemia.10,11 Nitrites, on the other hand, are a well known cause of methaemoglobinaemia, although the mechanism underlying this process has recently been disputed.12 Numerous cases have been reported worldwide, most commonly associated with drinking contaminated water6,13 or ingestion of meat products in which nitrite compounds have been used as a preservative.14,15 Both sodium and potassium nitrite are permitted for use in Australia in the preparation of processed meat, poultry and game products, where they are used both as a preservative and to improve appearance. However, their sale is prohibited for use in home cooking.16 Fortunately, in the cases reported here, all patients promptly sought medical attention, and there were no deaths or persistent adverse outcomes. The cases we report here highlight the need for accurate labelling of all potential food products and surveillance of these products to ensure that imported goods meet local standards. Overall, the recall delivered an effective and rapid response, with national media coverage (including community media in local spoken languages) and the alerting of hospital emergency departments. However, the cases also highlight potential problems in putting these measures into practice. Unlabelled or inappropriately labelled goods are able to slip into Australia undetected if they are not specifically imported as food additives. The Australian Quarantine and Inspection Service works with Food Standards Australia New Zealand on a national level, and the responsibility for products released into the marketplace passes to state and territory authorities. If improperly labelled goods have entered the country undetected and been locally distributed, coordination of their recall is complex, requiring cooperation of numerous parties across levels of government as well as bridging communication and cultural barriers. A packet of “Goldfish” brand “Nutre Powder”

Peter Maric MB BS(Hons) · Sayed S Ali MD · Leon G Heron FRCPA, FAFPHM · David Rosenfeld FRACP, FRCPA · Matthew Greenwood FRACP, FRCPA

Cryoglobulins are plasma immunoglobulins or immunoglobulin-containing complexes that precipitate on exposure to cold and redissolve on warming. They should be distinguished from red cell agglutinins and from the blood-component cryoprecipitates manufactured from donor plasma. The typical clinical triad of cryoglobulinaemia comprises purpura, arthralgia and weakness, with possible multisystemic organ involvement, notably glomerulonephritis and neuropathy. In blood smears prepared at room temperature, cryoglobulins can be detected by their peculiar morphology, which can assume globular, rhomboid or cylindrical amorphous precipitates (Figure, A–C, arrows; Wright–Giemsa stain, original magnification, × 200). Occasionally, these may be mistaken for blood cells, leading to spuriously high blood cell counts. Cryoglobulins are associated with infections (eg, hepatitis C), lymphoproliferative diseases and autoimmune diseases. Plasmapheresis is a useful adjunctive treatment for severe active disease, but the replacement fluid must be warmed to prevent precipitation of circulating cryoglobulins.

Herman H Lee · Chi-hung Hui

More than three-quarters of Australia is classified as geographically remote. Remote areas are characterised by geographic isolation, cultural diversity, socioeconomic inequality, resource inequity, Indigenous health inequality, and a full range of extreme climatic conditions. Although several descriptive definitions have been developed for “remote health” and “remote practice”, definitions of “remote medical practice” or “remote medicine” have not been previously published. In 2007, a working group of doctors and academics with experience in remote medicine was formed to develop the first advanced specialised remote medicine curriculum for remote doctors undertaking training with the Australian College of Rural and Remote Medicine. The first step was to define remote medical practice. Remote medical practice has eight key features: employment rather than private practice, isolation, use of telehealth, increased clinical acumen, extended practice, cross-cultural setting, multidisciplinary practice, and an emphasis on public health and personal security. From these eight features, we developed the first working definition of remote medical practice in the Australian context. Our definition will assist policymakers, medical colleges, standard setters, and educators to develop programs and resources for the future remote medical workforce.

Janie D Smith MPHC, EdD · Stephen A Margolis DRANZCOG, FRACGP, FACRRM · Jeff Ayton AFFTM, DRANZCOG, DA · Victoria Ross MB BS, FRACGP, MPHTM · Elizabeth Chalmers FACRRM, ACRRM, AFPHM · Patrick Giddings FACRRM, FRACGP, DRANZCOG · Louise Baker FRACGP, DRANZOC, DCH · Martin Kelly MB BS, PhD · Catherine Love MB, FACRRM, FRACGP

The strong interaction between the HIV and tuberculosis epidemics has been well described. Australian national surveillance data suggest that HIV status is ascertained by clinicians in less than 50% of people with tuberculosis. Clinicians are not able to reliably predict which people have HIV infection — risk factor assessment alone is insufficient. Because tuberculosis is an AIDS-defining condition and highly effective therapy for HIV infection is available, all patients with Mycobacterium tuberculosis infection should be offered HIV testing.

Carol R Emerson MB BCh, BAO, MRCP(UK) · Jeffrey J Post MB BS(Hons), FRACP

Clinical record A 67-year-old man presented to the rheumatology clinic with uncontrolled rheumatoid arthritis, which was being treated with leflunomide and prednisone. He had previously not responded to gold, methotrexate and cyclosporin. His other medical history included partial gastrectomy, diabetes mellitus and chronic renal impairment. In preparation for treatment with a tumour necrosis factor (TNF) receptor antagonist, a plain chest radiograph and tuberculin skin test were performed. The radiograph was clear, but the tuberculin skin response was strongly positive at 26 mm. The patient had received BCG vaccination more than 50 years earlier. His tuberculosis risk factors were a family history in his grandfather, and being from Eastern Europe. Given these findings, isoniazid was initiated for treatment of latent tuberculosis, with a proposed treatment plan of 6 months. Two months later, the patient presented with fever, night sweats and a painful left hip with reduced range of movement. Ultrasound showed a large collection extending from the hip joint. The hip joint aspirate showed a mild neutrophilic infiltrate, but no organisms were detected and polymerase chain reaction (PCR) testing for Mycobacterium tuberculosis was negative. Magnetic resonance imaging (MRI) of the hip revealed a large iliopsoas collection with femoral head signal changes and flattening (Figures). An infective cause was suspected, so arthroscopic lavage of the left hip and computed tomography (CT)-guided aspiration of the iliopsoas collection were performed. The aspirate removed 50 mL of fluid containing mildly increased neutrophils, but showed no evidence of M. tuberculosis by microscopy, culture or PCR. Nuclear technetium-99 scintigraphy showed uptake only in the femoral head, suggestive of osteonecrosis, with a differential diagnosis of osteomyelitis. A subsequent CT-guided biopsy of the psoas collection wall did not show any evidence of tuberculosis by histology, culture or PCR. At this stage, the patient’s rheumatoid arthritis was managed with prednisone 10 mg twice daily. He was started on a full anti-tuberculous regimen comprising rifampicin, isoniazid, pyrazinamide, and ethambutol, because of the highly positive tuberculin skin test and the large psoas collection. Two months later, a repeat CT scan showed resolution of the psoas collection, but persistence of the left hip effusion. The patient was treated with quadruple antituberculosis therapy for 2 months, but this was ceased because of diarrhoea secondary to Clostridium difficile. Over the next 4 months, several attempts to sequentially administer one to two antituberculosis medications were interrupted by recurrent episodes of pseudomembranous colitis caused by C. difficile infection, leading to total withdrawal of antituberculosis medications. Over the ensuing months, the left hip pain continued to worsen. Tuberculosis was still considered the most likely diagnosis and an arthroscopic biopsy of the left hip synovium was performed. This showed a non-specific chronic synovitis, but no granulomas and no acid-fast bacilli on PCR testing or culture. The patient underwent a total hip replacement 8 months after his initial presentation with left hip pain. Histology of the hip revealed osteonecrosis of the femoral head, synovial inflammation from rheumatoid arthritis and no evidence of tuberculosis. The iliopsoas collection was thought to be due to a giant iliopsoas bursa that did not recur after aspiration. Our patient had an enlarged iliopsoas bursa associated with osteonecrosis of the femoral head mimicking a tuberculous psoas abscess. Rheumatoid arthritis is a recognised cause of giant iliopsoas bursae.1-3 Other conditions leading to an enlarged iliopsoas bursa include acute trauma and overuse injuries. Infections can also result in iliopsoas bursitis or abscess formation.4 A number of organisms have been reported, with pyogenic bacteria, most commonly Staphylococcus aureus, implicated in most cases.5,6 Tuberculosis, once a well recognised causative agent of iliopsoas abscesses, is now less frequently reported in the Western world.6 Lessons from practice Patients with rheumatoid arthritis treated with anti-tumour necrosis factor (TNF) therapy have an increased risk of active tuberculosis infection. Specific screening tests should be done before initiating anti-TNF therapy. Latent tuberculosis remains a difficult diagnosis in the context of immunosuppressive illnesses or immunosuppressive therapy. Tuberculosis screening should ideally be performed early in the course of rheumatoid arthritis, particularly with aggressive disease. Iliopsoas bursitis related to rheumatoid arthritis may be confused with tuberculosis. Anti-TNF therapies are being increasingly used for treatment of inflammatory arthropathies, but can cause reactivation of tuberculosis.7 Patients with rheumatoid arthritis treated with anti-TNF agents have higher than background rates of tuberculosis, and are more likely to develop extrapulmonary or disseminated disease.8-10 There are mechanistic reasons why this may occur, specifically relating to inhibition of T-cell numbers and activation,11 as well as interference with granuloma formation.10,12 Assessment for tuberculosis in patients being considered for anti-TNF therapy should include clinical history, particularly previous tuberculosis exposure, prior tuberculosis treatment or BCG vaccination, physical examination, chest radiograph, and in appropriate cases, tuberculin skin testing.13 Patients with abnormal radiographs or who are at high risk should be assessed by a tuberculosis specialist. False positive tuberculin skin tests are seen both with previous BCG vaccination and with environmental mycobacteria.14 Interferon ? tests have the advantage of being less influenced by prior BCG vaccination and show stronger correlation in groups with tuberculosis exposure compared with tuberculin skin tests.14 A significant problem with tuberculin skin tests is the potential for false negative results in the context of immunosuppressive therapy. Patients on immunosuppressive treatment may also show increased rates of indeterminate results using the interferon ? tests.15 Latent tuberculosis is defined as having no signs or symptoms of tuberculosis, a positive tuberculin skin test (allowing for the specific clinical condition), and certain risk factors such as typical tuberculosis chest radiograph abnormalities or an immunosuppressive condition or treatment.14,16 In our patient, the tuberculin skin test was positive and he had both immunosuppressive disease and treatment. However, we found no tissue-specific histopathological or microbiological evidence for tuberculosis, despite multiple interventions. Current guidelines suggest that latent tuberculosis in the context of an abnormal chest radiograph should be treated either with isoniazid alone or with isoniazid and rifampicin, ideally before initiation of anti-TNF therapy.13 Of note, even after sustained prophylactic anti-tuberculous treatment, some patients may still develop tuberculosis reactivation following treatment with anti-TNF agents.13,17 Although the incidence of tuberculosis in patients from non-tuberculosis-endemic countries such as Australia is generally low,18 previously common extrapulmonary manifestations of tuberculosis such as iliopsoas abscesses may need to be considered more carefully once again. Furthermore, in patients treated with anti-TNF agents, given the imperfect screening tests for tuberculosis, especially in immunosuppressed patients, increased vigilance is needed for both extrapulmonary and disseminated tuberculosis. In this context, screening early in the course of inflammatory arthritis may be very useful.

David Massasso MB BS, BSc(Med), FRACP · Kevin Lee · Praneal Sharma FRANZCR · Fredrick Joshua MB BS, FRACP, PhD

Clinical record A 26-year-old recently married Filipino-born woman was referred to our hospital with left upper quadrant pain, vomiting and abnormal liver function test (LFT) results. There was nothing significant in her family history or past medical history. She described being unwell, and had lost 5 kg over 3 months, but had no respiratory symptoms or fever. On examination, she had slightly tender hepatomegaly palpable 3 cm below the right costal margin without any clinical stigmata of chronic liver disease. A BCG scar was noted. Her chest was clear and there were no other abnormal clinical findings. Her LFT results revealed elevated levels of alkaline phosphatase (345 U/L; normal range, 32–91 U/L) and γ-glutamyl transferase (215 U/L; normal range, < 38 U/L); other LFT results were normal. Findings of a full blood examination and urea, electrolytes and creatinine levels were all within normal limits. A triple-phase computed tomography scan of the liver was performed which showed hepatomegaly with multiple small, low-density lesions within the liver, which the reporting radiologist suggested may possibly be simple cysts. The appearance of the bowel, pancreas and lung bases were all normal. There was no intra-abdominal lymphadenopathy. Results of serological tests for hepatitis A, B and C were negative, as were results of tests for Wilson’s disease and α-1-antitrypsin deficiency, and antinuclear antibody, antimitochondrial antibody and antismooth muscle antibody. The patient subsequently underwent a liver biopsy, which revealed florid, non-caseating granulomatous reaction with aggregates of epithelioid histiocytes and Langerhans-type giant cells in a predominantly portal and periportal distribution (Figures A and B). The bile ducts were all intact and no evidence of malignancy was seen. Special stains, including Ziehl–Neelsen stain for acid-fast bacilli, were negative. The pathologist concluded that the histological appearance and distribution of granulomas was most consistent with the diagnosis of hepatic sarcoidosis. However, because of the patient’s ethnic background, further tests were undertaken to exclude tuberculosis (TB). A chest x-ray revealed clear lung fields and a normal mediastinal outline, with no indication of previous or current TB infection. A tuberculin skin test (TST) produced 12 mm of transverse induration. A QuantiFERON-TB Gold test (Cellestis International, Melbourne, Vic) was positive. As the TST and QuantiFERON-TB Gold test results were more in keeping with TB than sarcoidosis, the patient was treated for primary hepatic TB with quadruple therapy (isoniazid, rifampicin, pyrazinamide and ethambutol). Her clinical condition improved dramatically within a month of starting therapy, with a marked reduction in her hepatomegaly and normalisation of liver biochemistry. A retrospective polymerase chain reaction on the paraffin embedded tissue from the liver biopsy confirmed the presence of active TB within the liver specimens. Five months after completing the 9-month course of antituberculosis therapy, she was well and had recently become pregnant. Granulomatous hepatitis is an uncommon condition with a lengthy list of possible causes,1 as shown in Box 1. In our patient, the biopsy did not show bile duct destruction characteristic of primary biliary cirrhosis, or any evidence of malignancy. The patient was not taking any drugs which could cause granulomatous hepatitis. The pathology laboratory report suggested the diagnosis was sarcoidosis, and, of the infections that can cause granulomatous hepatitis, tuberculosis (TB) is the most common. Hence, although the differential diagnosis is long, the main clinical decision related to the ability to diagnose or exclude TB. If a patient with hepatic TB has corticosteroid therapy for erroneously diagnosed sarcoidosis, the consequences may be catastrophic. Active TB most typically presents with pulmonary symptoms, and the diagnosis can usually be made provided smears and cultures for mycobacteria are obtained. However, if a patient presents more atypically, as did our patient, clinicians may initially not suspect TB as the diagnosis.2 Lessons from practice It is critical to be certain that the cause of granulomatous hepatitis is not tuberculosis (TB) before commencing immunosuppressive medication. TB remains easy to diagnose if mycobacteria can be detected, but active TB is very difficult to exclude if cultures are negative or not performed. Risk of TB is determined by patient’s country of birth and duration of time spent there before migration.13 If TB cannot be excluded, a trial of antituberculosis therapy may be warranted. Tests used for the diagnosis of TB can be divided into two categories: the detection of a cell-mediated immune response to Mycobacterium tuberculosis (tuberculin skin test [TST] and QuantiFERON-TB Gold), and the detection of M. tuberculosis itself (by culture or polymerase chain reaction [PCR]). The TST is often falsely negative in immunosuppressed patients, and can give false-positive results if the patient has had previous BCG vaccination3 or infection with non-tuberculous types of mycobacteria. QuantiFERON-TB Gold is more specific for TB,4 but its sensitivity is poor, especially with immunosuppression.5 Both of these tests can be falsely negative in up to 20% of patients with active TB, and neither the TST nor the QuantiFERON-TB Gold test can distinguish between current, latent and previous (treated) infection. The only way to definitively diagnose active TB infection is by culturing the organism, or by detecting its nucleic acid sequence by PCR amplification from tissue or fluid samples. If active disease is suspected, specimens should be cultured for M. tuberculosis whenever possible, as a positive result confirms the diagnosis and allows drug sensitivity tests to be performed. While the diagnosis of active TB can be confirmed by PCR, this is not necessarily as sensitive as culture, and does not allow drug sensitivity testing.6 In our patient, the mycobacterium was confined to the liver, which was unusual. It is far more common to have TB involvement of the liver in disseminated TB.7 Ideally, the liver biopsy should have been sent for culture in a TB medium, but we did not suspect TB initially. Once fixed in formalin and paraffin, the tissue cannot be cultured, but PCR of M. tuberculosis DNA can still be performed on the specimen and may yield a diagnosis.8 Histological examination of liver tissue provides crucial information in the differential diagnosis of hepatic granulomas. While caseous necrosis is characteristic of TB infection, it is not always present and its absence cannot be used to exclude TB.7 Also, as it is often difficult to detect the presence of acid-fast bacilli (AFB) within the granulomas, the absence of AFB cannot be used to exclude TB either.9 In Australia, the incidence of TB is six per 100 000 per year,10 compared with the incidence of sarcoidosis, which is estimated at 20 per 100 000 per year worldwide;11 sarcoidosis is thus the more likely cause of hepatic granulomas in Australian-born patients. However, the incidence of TB in the Philippines is 291 per 100 000 per year,12 making TB the far more likely cause of hepatic granulomas in our Filipino-born patient. We believe that if the diagnosis of TB cannot be excluded, and the patient has risk factors for TB, it is appropriate to initiate antituberculosis therapy. However, clinicians should not make this treatment decision lightly, because antituberculosis drugs have a significant side-effect profile. 1 Causes of granulomatous hepatitis Autoimmune Sarcoidosis Primary biliary cirrhosis Systemic infections Mycobacterial — tuberculosis Fungal — cryptococcosis Rickettsial — Q fever Zoonotic — brucellosis Malignancy Hodgkin’s disease Non-Hodgkin’s lymphoma Renal cell carcinoma Drugs Allopurinol Sulphur drugs Quinidine Other drugs Idiopathic

Eu Jin Lim MB BS · Paul D R Johnson MB BS, FRACP, PhD · Peter Crowley MB BS, FRCPA · Paul J Gow MD, FRACP

Tumour necrosis factor (TNF) α inhibitors such as infliximab are becoming more widely used for the treatment of selected patients with Crohn’s disease, rheumatoid arthritis, and other inflammatory disorders. TNFα inhibitors increase the risk of serious infections, including tuberculosis. Screening for and treatment of latent tuberculosis infection before infliximab therapy reduces the risk of developing active tuberculosis. New blood tests that measure interferon γ production are an alternative to traditional tuberculin skin testing and offer some significant advantages over skin testing for screening of latent tuberculosis infection.

Arun Gupta MB BS · Alan C Street MB BS, FRACP · Finlay A Macrae MB BS, MD, FRACP

The burden of illness from herpes zoster (HZ) and postherpetic neuralgia (PHN) in the Australian community is high. The incidence and severity of HZ and PHN increase with age in association with a progressive decline in cell-mediated immunity to varicella-zoster virus (VZV). Antiviral medications (valaciclovir, famciclovir, aciclovir) have been shown to be effective in reducing much but not all of the morbidity associated with HZ and PHN, but are consistently underprescribed in Australia. Zoster-associated pain should be treated early and aggressively, as it is more difficult to treat once established. Clinicians should be proactive in their follow-up of individuals at high risk of developing PHN, and refer patients to a specialist pain clinic earlier, rather than later. A live, attenuated VZV vaccine (Oka/Merck strain, Zostavax [Merck Sharp & Dohme]) has proven to be efficacious in reducing the incidence of and morbidity associated with HZ and PHN in older adults. The vaccine’s efficacy has been shown to persist for at least 4 years, but is likely to last a lot longer. Ongoing surveillance will determine the duration of protection and whether a booster dose is required. Clinicians should consider recommending the vaccine, which can be safely administered at the same time as the inactivated influenza vaccine, to all immunocompetent patients aged 60 years or older. Clinicians should refer to the Australian immunisation handbook for advice on the use of the live vaccine in immunosuppressed individuals.

Anthony L Cunningham MD, FRACP, FRCPA · Judith Breuer MD, MB BS, FRCPath · Dominic E Dwyer MD, FRACP, FRCPA · David W Gronow FFARACS, FANZCA, FFPMANZCA · Robert D Helme PhD, FRACP, FFPMANZCA · John C Litt MSc(Epid), FAFPHM, FRACGP · Myron J Levin MD · C Raina MacIntyre FRACP, FAFPHM, PhD

Objective: To provide data on the career trajectories of medical students from rural and remote workforce programs at Flinders University (the Parallel Rural Community Curriculum [PRCC] and the Northern Territory Clinical School [NTCS]), comparing them with students at the urban Flinders Medical Centre (FMC).Design: Retrospective postal survey of all 150 graduates who undertook their Year 3 study in the period 1998–2000.Outcome measure: Associations with career preference, assessed using univariate analyses and multivariate regression.Results: PRCC and NTCS graduates were more likely to choose rural career paths than graduates from FMC. The odds ratios were 19.1 (95% CI, 3.4–106.3; P < 0.001) and 4.3 (95% CI, 1.2–14.8; P = 0.026), respectively, after adjusting for age and rural background. There was no difference in the specialty choices of graduates of the three programs.Conclusion: This study provides evidence that clinical attachments designed to increase the rural and remote medical workforce do fulfil this objective.

Paul Worley MB BS, FRACGP, FACRRM · Anne Martin PhD · David Prideaux BEd, PhD · Richard Woodman PhD, MBiostat, MSportsSci · Elizabeth Worley BN, MEd, GradCertCounsel · Michael Lowe MB BS, FRACP

The medical schools at the University of Western Sydney, University of Wollongong and University of Sydney have developed a joint program for training medical students through placements of up to 40 weeks on the New South Wales North Coast. The new partnership agency — the North Coast Medical Education Collaboration — builds on the experience of regional doctors and their academic partners. A steering committee has identified the availability and support requirements of local practitioners to provide training, and has undertaken a comparative mapping of learning objectives and assessments from the courses of the three universities. The goals of the program include preparing doctors who can perform effectively in rural settings and multidisciplinary health care teams, and to advance research in medical education.

Sue L Page BMed, FRACGP, FACRRM · Hudson H Birden MPH · J Nicky Hudson BM BS, MSc, PhD · Jill E Thistlethwaite MB BS, PhD, MMEd · Chris Roberts MB ChB, MMedSci, PhD · Ian Wilson MB BS, PhD, FRACGP · John Bushnell PhD · John Hogg MB BS, PhD · S Ben Freedman MB BS, BSc(Med), PhD · Neville Yeomans MB BS, MD

Sexually transmissible infections (STIs) are hyperendemic in some remote Indigenous populations in Australia. Screening programs have had some success in reducing the prevalence of STIs in specific populations, but there has been little overall improvement in the past 10 years. We question the usefulness of current practice and urge consideration of a new and radical approach. Instead of a “screen, treat and contact trace” strategy, we suggest adopting the same approach as currently accepted for trachoma control: populations reaching a threshold prevalence for a set of marker STIs (identified through sentinel surveillance) should be offered a treatment program aimed at the entire sexually active population. We also recommend a parallel program of health promotion and “life skills” education and outline the arguments for such a departure from currently accepted public health policy.

Francis J Bowden FRACP, FAChSHM, MD · Katherine Fethers MB BS, FAChSHM, MMed(STD/HIV)

To the Editor: In the recent article by Richards and Rogers, the ethical and legal arguments made to justify antemortem interventions for organ donation after cardiac death (DCD) raise some questions.1 First, do antemortem interventions harm the patient? Anticoagulants (eg, heparin) expand intracranial haemorrhage and hasten the death of potential donors with acute ischaemic or haemorrhagic strokes. Large volumes of crystalloid fluids are infused to maintain organ perfusion, while exacerbating cerebral oedema and accelerating the onset of brain stem herniation and infarction in potential donors. Vasodilators are infused for organ preservation, causing hypotension and early onset of cardiorespiratory arrest after discontinuation of mechanical ventilation. While it may be debatable whether these interventions can cause harm to a person destined to die, they certainly shorten the dying process and hasten death.2 Many cultures and societies worldwide consider the performance of interventions to shorten the dying process ethically unacceptable.3 In the United States, the intent to administer — for the sole purpose of organ viability — a medication that expedites death and shortens the warm ischaemia time in DCD is a criminally liable action.4 Regardless of the lack of evidence that dying in an operating theatre is not worse than dying in an intensive care unit, if dying in the operating theatre results in the denial of death with dignity and peace, it can result in long-lasting traumatic experiences and memories for families and relatives.5 Second, is consenting to appendicectomy the same as consenting to organ donation? The only similarity between appendicectomy and removal of organs from a donor is that both are surgical procedures performed in the operating theatre. However, consent to the former is intended to “heal and preserve life” while the latter has no such intent and can imply to “shorten life”. To draw a conclusion that consent to DCD could be viewed as consent to take all reasonable steps to ensure that the operation is successful and results in the procurement of viable organs for transplantation is only justifiable if society has decided to abandon the “dead donor rule” and sanction “physician-assisted suicide”.2

Mohamed Y Rady · Joseph L Verheijde · Joan L McGregor

To the Editor: Richards and Rogers1 claim that antemortem interventions on an organ donor to improve organ viability for donation after cardiac death (DCD), such as administration of heparin and femoral vessel cannulation, are ethically and legally justified. Their reasoning is flawed. Their ethical argument is twofold. First, they argue that, just as consent for appendicectomy is broad and does not encompass details of the operation, so too the consent for organ donation is broad and does not exclude antemortem procedures. This is drawing a long bow. While details of appendicectomy are in the patient’s best interests while alive, interventions performed on a potential donor while alive for organ procurement after his or her death are not. It would be clear to potential donors signing a consent form giving permission for organs to be harvested after they die that they are not also giving permission for procedures to be performed while still alive. If potential donors discover that interventions which may hasten or contribute to their death could be done on them without their express consent, adverse publicity would reduce organ donation. Not only is the proposal disingenuous, it would be challenging indeed to find a potential donor willing to be harmed by treatment in order to be the donor of better organs! The authors’ second ethical argument, which relies on a conference report,2 is: There is no evidence that, in the absence of active bleeding, administration of heparin would cause sufficient bleeding to contribute to death.1 The underlying assumption is that full heparinisation carries no risk. This is wrong — major haemorrhagic complications of even therapeutic heparinisation have long been recognised.3 Moreover, the conference report also stated: The appropriate timing for administration of anticoagulants and vasodilators during the DCD process is unresolved. Flushing organs with anticoagulants/vasodilators after procurement may be as effective as pre-procurement administration.2 Thus, their argument is based on a statement taken out of context and against evidence. Ethical guidelines on the subject conflict. The National Health and Medical Research Council (NHMRC) guidelines state that: Where the law permits, it is ethical to proceed with these [antemortem] interventions if: ... interventions will not contribute to the cause of death or compromise the continuing care of the patient.4 In contrast, section 2(6)(h)(i) of the New South Wales Health guidelines5 advises against the use of antemortem interventions, because they would unlawfully contravene section 46(2)(b) of the Guardianship Act 1987 (NSW), which restricts guardians to consenting to treatments with the purpose of “promoting or maintaining the health and well-being” of the person involved. Whether one agrees or disagrees with either guideline, they do not constitute law.6 Richards and Rogers’ legal argument relies merely on fulfilment of a donor’s desire to be an organ donor as justification under the various Guardianship Acts. However, this argument can only apply when the antemortem interventions are not harmful to the potential donor; heparinisation is potentially harmful, and femoral vessel cannulation is clearly harmful. The NSW guidelines are criticised for interpreting the patient’s best interests requirement of the Guardianship Act too narrowly, and therefore do not constitute a reason to not perform antemortem interventions. But I consider this argument to be hoisted on its own petard: it is equally too narrow to focus on the wishes of the patient to be a donor as justification to perform antemortem interventions. The legal requirement is clearly illustrated in the Guardianship and Administration Act 1986 (Vic), which stipulates that a guardian must take account of all of several factors in determining if a treatment is in the patient’s best interests (Box). Lastly, an attempt is made to buttress the legal argument by reference to Airedale NHS Trust v Bland, in which the House of Lords permitted withdrawal of life-sustaining treatment to allow a man in a persistent vegetative state to die. Since the Lords considered best interests to include wider interests than continuance of futile treatment, Richards and Rogers, by analogy, believe that this concept is sufficient to justify performance of antemortem interventions on potential donors. In fact, the House of Lords did not base their decision on best interests, but rather on “the futility of the treatment which justifies its termination”.7 Comments by the Lords about other best interests did not form part of the court’s decision and so do not constitute law, cannot be invoked in other circumstances, and in any case, do not apply to Australian jurisdictions. There is neither ethical nor legal justification to perform antemortem interventions on a potential donor for the benefit of a recipient. Noble as the proposal may first appear, it is a Rubicon not to be crossed. Guardianship and Administration Act 1986 (Vic), section 38(1) To determine a patient’s best interests, a guardian must consider: (a) the wishes of the patient, so far as they can be ascertained; and (b) the wishes of any nearest relative or any other family members of the patient; and (c) the consequences to the patient if the treatment is not carried out; and (d) any alternative treatment available; and (e) the nature and degree of any significant risks associated with the treatment or any alternative treatment; and (f) whether the treatment to be carried out is only to promote and maintain the health and well-being of the patient; and (g) any other matters prescribed by the regulations.

James Tibballs

To the Editor: In their recent article,1 Richards and Rogers connect some ideas about patient autonomy, non-maleficence and laws relating to consent with specific antemortem activities, but their main “justification” for these activities is a practice termed donation after cardiac death (DCD). This practice has been introduced in the hope of increasing the availability of organs for transplant. It involves removing cardiorespiratory support and withholding resuscitation, then harvesting organs when cardiac death occurs.2,3 As illustrated by the New South Wales Health DCD guidelines (Box), DCD represents a significant shift in practice — from maintaining cardiorespiratory support for the purpose of organ preservation after an acutely injured patient has died (the brain death scenario), to removing life support with the explicit intention of allowing expeditious death and organ removal (the cardiac death scenario).3 There are two facts of clinical practice that I suggest should be taken into account in the ethical or legal justification of any DCD-related activity and also before the “re-introduction of expanded use of DCD” and “introduction of a NSW DCD program” mentioned in the NSW guidelines.3 The first is medical: the earlier a prognostic call is made in relation to catastrophic injury, the greater the chance it could be wrong. The second is psychological: doctors treating severely injured patients are aware of the need for organs in good condition and the importance of opportunity, and generally appreciate that organ transplant programs are one way that good can come out of tragedy. These simple facts are ethically and legally problematic because they could increase the probability of overcalling the extent and permanency of injury in an acutely injured patient, which in turn increases the probability of the patient being denied his or her chance to survive. Accordingly, any ethical or legal justification for submitting an injured patient to any antemortem activity relating to harvesting their organs after death — including withdrawing cardiorespiratory support and withholding resuscitative efforts — requires safeguards that protect the treatment paradigm for the patient. This requires two things: demonstrating that the care of the patient is not being compromised by his or her donor status; and making consent (in the full sense of the term) inviolate. I would argue that the former is impossible in the acute severe injury scenario of DCD, and the latter requires a legal step between end-of-life decisions and end-of-life action of the kind referred to by Justice O’Keefe in Northridge v Central Sydney Area Health Service, with respect to withdrawal of life-sustaining treatment and medical support from patients in a persistent vegetative state.4 As O’Keefe noted of such cases in the United Kingdom, where there are clear guidelines regarding lawful withdrawal of treatment: [T]he requirement that termination of treatment, artificial feeding and hydration be only with the prior sanction of a High Court judge, is a clear recognition of the right of unconscious patients to have their right to life protected by the full power of the law.4 Extract from the New South Wales Health guidelines3 Donor Category 3 Waiting cardiac death after planned treatment withdrawal – Known and limited warm ischaemic time: “Controlled” Donor selection criteria, point 3 Catastrophic, irreversible cardiorespiratory or neurological injury, not fulfilling brain death criteria, where withdrawal of life sustaining treatment is considered appropriate and following which rapid progression to death is anticipated.

Judith R Kennedy

In reply: The issues raised by Rady and colleagues, Tibballs, and Kennedy include claims that antemortem interventions for organ donation after cardiac death (DCD) are harmful, involve inadequate consent procedures, and require abandoning the “dead donor rule”. To clarify, we advocate the use of antemortem heparin in people with a known desire to be organ donors; we do not advocate potentially harmful or disruptive interventions such as femoral vessel cannulation. Rady and colleagues cite their recent article1 to support the claim that antemortem interventions are harmful. However, that article makes no reference to antemortem interventions such as heparin hastening death. In contrast, Bernat et al clearly state: The use of heparin is considered controversial on the basis of theoretic concerns that it may hasten the death of the donor. Nevertheless, there is no evidence that heparin causes sufficient bleeding after withdrawal of treatment and thus, causes death.2 (emphasis added) This position is supported by international evidence-based protocols that advocate the use of antemortem heparin, such as those from Britain3 and Canada.4 Rady and colleagues’ claim that antemortem interventions are criminal in the United States seems to relate to a US surgeon who was charged with murder after allegedly administering 200 mg of morphine and 80 mg of lorazepam to hasten patient death in a failed DCD case.5 These drugs are standardly used in therapeutic doses for end-of-life care. Our proposal supports best practice end-of-life care; we do not suggest this care should be delivered by the transplant surgeon. The example of one apparent rogue practitioner is not evidence that antemortem interventions are unethical. We agree with Tibballs that the wishes of the patient constitute only one of many elements listed in the various Guardianship Acts that should be taken into account when determining best interests. However, we are aiming at the spirit of the law rather than the narrower “black letter” view, as this ignores the situation of dying patients whose physical interests are extremely limited, leaving their wishes as the final expression of their humanity. With respect to Tibballs’ assertion that Airedale NHS Trust v Bland is not law in Australia, we acknowledge that it is not binding, but the persuasiveness of the judicial reasoning of the House of Lords has been well recognised and has provided guidance and been cited with approval in numerous decisions in Australia. Recent examples include Harriton v Stevens6 and Application of Herrington, re King.7 In relation to Kennedy’s comments about Northridge v Central Sydney Area Health Service, this difficult case (in which there was disagreement between hospital doctors and the patient’s family about treatment withdrawal) can be distinguished from our argument. We do not advocate acting contrary to the wishes of a patient’s family members. With DCD, the decision to withdraw treatment is made by the family and treating doctors independently of and before any discussions about donation. We recognise the potential psychological stresses involved in caring for patients in this situation. Clarity about what is legally and ethically acceptable, and clear separation of decisions to withdraw treatment from discussions about donation may help to alleviate some of this stress. We do not advocate hastening or redefining death, nor do we suggest abandoning informed consent. We believe, for the reasons given in our article, that non-harmful antemortem interventions are legally and ethically justifiable.8

Wendy A Rogers · Bernadette J Richards

To the Editor: Russell and colleagues recently wrote an open letter to the new Minister for Health.1 In response, we call for the Minister to champion the cause of Indigenous health. Dear Minister,Russell et al raise a number of pressing issues directly relevant to the health portfolio.1 However, of all the challenges that face you, perhaps the greatest is reversing the neglect and extreme health disadvantage experienced by Australia’s Indigenous people.2 Although the task is daunting, and detractors may argue that there are no evidence-based solutions, 150 years of collective experience from across the globe provides compelling support for real investment in the spheres of water, sanitation, housing, education, employment and primary health care to reverse health disadvantage. Tragically, while these basic necessities are taken for granted by most Australians, they remain a dream for many Aboriginal and Torres Strait Islander peoples. The greatest public health gains during the previous two centuries resulted from ensuring that communities had sustained access to clean water, adequate sanitation and appropriate housing.3 It is astonishing that these basic rights should remain on the unresolved agenda of a highly developed country. To our shame, these basic direct health determinants are not yet guaranteed for Aboriginal and Torres Strait Islander Australians.4 Relative poverty, absolute poverty and social exclusion all have a major impact on health.5 In Australia, relative poverty denies many Indigenous communities access to housing, education, transport and other societal benefits. It would be naïve to argue that this inequitable distribution of Australian resources has not been a major determinant of the poorer health of Indigenous Australians.6 The recent Auditor-General’s report on whole-of-government Indigenous service delivery arrangements clearly indicates that current approaches are inadequate and fall short on service delivery.7 There is therefore a critical need for decisive direct investment in basic infrastructure and its maintenance in Indigenous communities, along with comprehensive primary health care. This must extend to equipping and developing individuals and communities through a major investment in education and creation of employment opportunities that engages the community and is developed in true and equal partnership with respected Indigenous leaders and communities You may argue that many of these health determinants fall beyond your direct sphere of accountability. You may choose to point to the small-scale success stories, particularly in Indigenous primary health care. However, as Minister for Health and Ageing, you will continually be confronted by the direct evidence of the deleterious results of these health determinants on the life expectancy and health of Indigenous Australians.8 The time is ripe for a bold national leader to champion this cause in the corridors of power. We encourage you to become that advocate among your Cabinet colleagues. The challenge is yours. Will you have the courage and moral fortitude to make your mark on Australian history?

David N Durrheim · Mark Wenitong · Clare Huppatz · George Rubin

To the Editor: The academic success of the rural clinical schools (RCS) program is clear: community-based clinical placements in rural Australia are able to produce graduates that are academically indistinguishable from tertiary hospital-trained peers.1,2 The effect of the RCS program on the workforce is yet to be established. Eley and Baker recently identified early career choices by Queensland RCS graduates.3 Western Australian RCS students spend an entire academic year in the country. Here, we provide the first data on the return of WA RCS graduates to rural internship positions relative to the intern year cohort as a whole. Based on two cohorts entering postgraduate year 1 (PGY1) positions in 2004 and 2005, 14 of 28 WA RCS graduates have requested and completed the one rural rotation that is permitted during their intern year. Given the limited rural rotations available in WA, some sought rural experience as far afield as Queensland and New South Wales. The substantive uptake of rural experience by RCS interns is in contrast to the intern cohort as a whole (Box). In 2004 and 2005, the three WA tertiary allocation centres placed 135 and 131 interns, respectively. As WA has no whole-year rural internships, a subset of the urban allocation included a 3-month rural rotation. The distribution of graduates of the RCS was different to that of graduates from other programs (χ2 = 7.0693; df = 1; P = 0.008). RCS students were more likely than other graduates to take a rural rotation (odds ratio, 3.1). Furthermore, ongoing postgraduate contact with the RCS cohort has identified that 23 of 28 graduates have chosen to undertake at least some time in the country during their PGY1–3 years. There is also early indication that graduates will sign up for a rural vocational training pathway (3/28). Interestingly, only a small proportion of these graduates are from a rural background (5/28). Our data suggest that rural practice is seen as highly desirable postgraduate clinical experience by WA RCS graduates. These results provide initial evidence that the WA RCS program will increase the rural workforce. Aggregate of 2004 and 2005 rural clinical school (RCS) interns versus non-RCS interns: comparison of postgraduate year 1 (PGY1) intern location choices RCS (n = 28) Non-RCS (n = 238) Total (n = 266) Expected tertiary allocation centre PGY1 internships (statistically even distribution) Urban-only internship 20 174 194 Rural rotation during internship 8 64 72 Actual tertiary allocation centre PGY1 internships (actual distribution) Urban-only internship 14 180 194 Rural rotation during internship 14 58 72

Denese E Playford · Harriet Denz-Penhey · Lesley Skinner · J Campbell Murdoch

To the Editor: The growing problem of tuberculosis in resource-rich countries has been recently highlighted,1 with immigration thought to be an important contributor. To assess a possible increase in incidence, we performed a retrospective case record review of all children who had tuberculin skin tests or who were diagnosed with tuberculosis at The Children’s Hospital at Westmead for 3 years from 2004 to 2006. This period included the establishment of a refugee clinic in May 2005, which routinely tests refugees by tuberculin skin testing. We compared our findings with published data from 1982 to 1991.2 Latent tuberculosis infection was defined as tuberculin skin test induration of ≥ 10 mm (regardless of prior BCG vaccination) and a decision by the treating physician to start isoniazid monotherapy. Proven active tuberculosis disease was defined as a child with a positive isolate of Mycobacterium tuberculosis from culture or positive polymerase chain reaction for tuberculosis or positive tuberculin skin test in association with a clinical picture strongly suggestive of active tuberculosis disease. The number of tuberculin skin tests performed increased through the study period (Box 1), largely because the refugee clinic saw 90 new patients in 2005 and 150 in 2006. The proportion of children with an increased induration response increased over the study period (Box 1 and Box 2). We observed an increase in latent tuberculosis infection, both in absolute numbers and in the proportion of the total caseload. The absolute number, but not the proportion, of cases of active tuberculosis disease increased during the study period. Over the same period, hospital admissions remained static at about 26 000 per year. Extrapulmonary tuberculosis was present in 12 of 23 patients (52%) with active tuberculosis, compared with 34% in the earlier study.2 There was no increase in tuberculosis meningitis. The active tuberculosis cohort ethnicity was consistent with the earlier study, with 22 of 23 patients of non-European origin, and 18 born outside Australia. The predominant ethnic groups were from Africa (eight, all born outside Australia) and the Indian subcontinent (four, two born outside Australia). Our finding of an increase in the proportion of patients with latent tuberculosis infection but not active tuberculosis disease is largely due to increased testing of refugees. It is reassuring that we did not find active tuberculosis. The United Kingdom has reported an increased incidence of tuberculosis in African immigrants.1,3 Australian immigration trends have shown a demographic shift, with increasing numbers of refugees from Africa.4 Although our study is likely to suffer from referral bias, it is the largest review of paediatric tuberculosis from a tertiary centre in Australia. Children very rarely transmit tuberculosis, but it is important to identify and treat latent tuberculosis to prevent progression to active disease.5 We believe our results are encouraging in showing a low incidence of active tuberculosis and indicate the need to screen refugees for latent tuberculosis to direct chemoprophylaxis. 1 Comparison data on tuberculosis among children, 2004–2006 Year Total TSTs performed Results available > 10 mm > 15 mm No. of patients commenced on isoniazid No. with active TB disease No Yes No Yes 2004 116 111 104 7 108 3 5 4 2005 257 247 202 45* 221 26* 25 8 2006 278 263 193 70* 215 48* 36 11 TST = tuberculin skin test. TB = tuberculosis. * P < 0.01 compared with previous year. The discrepancy between the total numbers performed and the cumulative numbers in the categorisation of response is due to patients not returning to have the TST read. 2 Results categorised by size of tuberculin skin test induration

Paul D Robinson · Dianne Dalton · Terri Cripps · Nicholas J Wood · Alison M Kesson · David Isaacs

To the Editor: I write to voice my objection to the use of the term “tsunami” by many in the medical education community when describing the massive increase in medical student numbers that has begun as a result of recent government initiatives.1-5 Although it is true that the government has opened the floodgates, as opposed to the water restrictions they applied in the mid 1990s, I believe describing this increase using the metaphor of a tsunami is a misnomer. I do not disagree with the potential for this phenomenon to wreak mayhem with the quality teaching and supervision of medical students and junior doctors and their access to adequate employment in both prevocational and vocational places. Nevertheless, I believe that we need to adopt a more accurate term to describe this impending event. A term I have heard on a number of occasions is that of the “rising sea levels” of medical graduates, which (although less dramatic) I think is more accurate, because this expression indicates that the change (likely a sea change) is going to be long-lasting, if not permanent, rather than a flash flood, as signified by “tsunami”. If we are going to continue to describe this impending increase as a “tsunami”, the only benefit I can see is that it may encourage us to learn lessons from the real event. As a result of the 2004 Boxing Day tsunami, a tsunami early warning system was put in place to alert citizens of an impending tsunami and give them a small window of time to prepare. A number of medical education groups, including the Australian Medical Association Council of Doctors in Training, have started sounding the alarm about the increase in medical students. It remains to be seen whether this warning will be heeded in time. One only has to look to the fiasco in the United Kingdom this year with junior doctor allocations to see what happens when adequate preparation is not made for impending change. Will a student who enters medicine in 2010 feel that, during their medical education voyage, they are receiving a quality education? And when they graduate, will they find a rich sea of prevocational and vocational opportunities? Or will they feel like a drop in the ocean of fellow graduates scrambling to gain a properly supervised training position?

Andrew W Perry

Attacking anaphylaxis Platelet-activating factor (PAF) and PAF acetylhydrolase have been identified as important mediators of anaphylaxis in humans, according to Canadian researcher Vadas and colleagues. PAF is a proinflammatory phospholipid secreted by mast cells, monocytes and fixed tissue macrophages; PAF acetylhydrolase is the enzyme that inactivates PAF. In a two-part study, they found that: (1) mean serum PAF levels were not only higher in 41 patients with anaphylaxis than in 23 healthy volunteers but were also correlated with the severity of anaphylaxis; and (2) that serum PAF acetylhydrolase activity was lower in nine patients with fatal peanut anaphylaxis than patients in any of several control groups. They suggested that failure of PAF acetylhydrolase to inactivate PAF may contribute to the severity of anaphylaxis. The researchers said further studies will be needed to assess the usefulness of PAF acetylhydrolase as a biochemical marker of risk for anaphylaxis. They also said that their data provide a rationale for the development of drugs to selectively block the actions of PAF — both as rescue therapy in cases of acute anaphylaxis and, potentially, as long-term preventive treatment for those at highest risk for fatal anaphylaxis. N Engl J Med 2008; 358: 28-35 Facing up The world’s first full facial transplant could finally happen in the United Kingdom this year, according to a feature article in the BMJ. Adopting an evidence-based research strategy, pioneering plastic surgeon Peter Butler’s London-based team has now gained approval to conduct a clinical series of four full facial transplants. A small group of recipients have been identified, including casualties from the armed forces injured on duty in Iraq. The next phase is to look for a suitable well matched donor face, so that the donor is not “seen” in the recipient. Each transplant operation will involve about 35 professionals, and will be funded by Butler’s charity, the Face Trust. BMJ 2008; 336: 18-19 Fallout follows deluge When Hurricane Katrina hit New Orleans on 29 August 2005, the city’s hospital staff struggled to care for patients for several days afterwards, without power (and air-conditioning), fresh water or functional sanitation. Now, an article reports that one of the doctors who “stayed behind” to help faces three civil suits after reportedly administering morphine and midazolam to several critically ill patients who subsequently died. Due to the litigation, details have not been publicly discussed; however, as it stands, the incomplete story suggests that civilian doctors were expected to make difficult triage, evacuation and other decisions when working with limited resources in conditions more closely resembling those of a battlefield than a hospital; miscommunication may also have played a part in events. Although a grand jury has previously refused to indict the doctor involved, there has been at least one prediction that efforts to prosecute the doctor will have a chilling effect on the willingness of medical professionals to volunteer during disasters. It is suggested that expanded training and public debate about triage, communication and decision making in disasters could help all of us to better prepare for any ordeals of the future. N Engl J Med 2008; 358: 1-5 Be a doctor in 3 years? How long does it take to become a doctor? How long should it take? For about 30 years, two universities in Canada — McMaster University in Hamilton, Ontario and the University of Calgary — have been training people to become doctors in just 3 years, whereas all the other medical schools in Canada offer a 4-year program. Given the high professional and social costs of a further year of study, CMAJ editors say that it is time to formally examine whether the “extra” fourth year is really needed. They suggest comparing the 3-year and 4-year programs in terms of, first, short-term outcomes — particularly medical licensing examination scores — and second, long-term outcomes — such as the proportion of graduates in leadership roles, the proportion serving areas of greatest need, and the proportion subject to licence restrictions or disciplinary actions. CMAJ 2008; 178: 11 Obesity and gum disease Researchers in the United States have shown that obesity interferes with the ability of the immune system to respond to bacterial infection. In animal research, Amar and colleagues infected (diet-induced) obese mice and lean control mice with live Porphyromonas gingivalis, an organism strongly associated with periodontitis in people. The mice were infected with the P. gingivalis either orally or systemically; in both cases, the obese mice developed a blunted systemic inflammatory response, including reduced levels of pro-inflammatory cytokines. The researchers suggested that strong antimicrobials rather than anti-inflammatory agents should be used in individuals with diet-induced obesity and severe infection. Proc Natl Acad Sci U S A 2007; 104: 20466-20471

Ann Gregory