Infectious diseases

Kristine Macartney,* Peter McIntyre† * Senior Research Fellow, † Director, National Centre for Immunisation Research, The Children’s Hospital at Westmead, Locked Bag 4001, Westmead, NSW 2145. petermATchw.edu.au Comment: Recently published data have added considerably to the evidence about the impact of varicella vaccination programs, and address many of the concerns raised by Mackenzie. First, in the United States where universal varicella vaccination was recommended a decade ago, recent data show that — despite much slower implementation than is expected in Australia — varicella-related disease has declined by up to 90%, and hospitalisation rates and deaths from varicella by more than two-thirds, due to herd immunity.1,2 Second, data have now been published on the incidence of herpes zoster in areas of sentinel surveillance in the US, showing no change in age-specific rates to 2002.3 Along with the success of a recent trial of high-dose varicella vaccine in reducing herpes zoster in older adults,4 these data add to confidence that any increase in herpes zoster — as predicted in some models — will be detected and effectively combated by vaccinating people aged over 60 years. A substantial allowance for surveillance of both varicella and herpes zoster was included in the 2005 federal budget, to accompany the introduction of universal varicella vaccination in Australia. Mackenzie is correct that varicella is perceived by some as a mild illness, but it is important for general practitioners to emphasise to patients that this is incorrect.5 Each year in Australia, varicella causes around seven to eight deaths and more than 1500 hospitalisations,6 many associated with serious complications, such as invasive bacterial infection, pneumonia, and encephalitis. Although complications are more likely in adults and immunocompromised patients, 42% of hospitalisations are in children aged 0–4 years,6 most of whom are otherwise healthy.7 Patients can also be reassured about the safety of varicella vaccines, as clinical trials now date back 30 years, and more than 40 million doses of vaccine have been distributed in the US. Mackenzie suggests alternatives to universal childhood varicella vaccination, such as vaccination of “high risk” patients and their families, or of adolescents alone. However, these programs would not prevent morbidity among otherwise healthy young children and older age groups, as they would be insufficient to generate herd immunity. Moreover, age-based vaccination strategies have been shown to be easier to implement than more targeted programs. In the absence of a publicly funded universal program, the private market could sustain modest varicella vaccination rates of around 40%–50% in Australia.8 This would increase the number of adolescents and adults susceptible to varicella, because of reduced exposure to the virus and lack of vaccination; these groups also experience greater morbidity with infection than children. A universal program vaccinating young children and adolescents against varicella offers the best current option to reduce morbidity and mortality from this disease in Australia. Ongoing surveillance of varicella and herpes zoster in Australia and elsewhere will reveal whether there is a need for further interventions, such as a second dose of varicella vaccine in children and high-dose varicella vaccine to prevent herpes zoster in older adults.

Kristine Macartney · Peter McIntyre

Re: the letter “Reliability of parental reports of head lice in their children”, by Megan L Counahan, Ross M Andrews and Rick Speare, in the 7 February issue of the Journal (Med J Aust 2005; 182: 137-138). There was an error in Box 2, Sensitivity and specificity of parental report versus screening. The specificity given as 94.0% (969/1030) should have been 98.8% (1018/1030). The html and pdf versions of this article published online were corrected on 5 August 2005.

Megan L Counahan · Ross M Andrews · Rick Speare

Fighting the current epidemic requires intensive education of clinicians and men who have sex with men, as well as targeted screening A research article (page 179)1 and a letter to the editor (page 218)2 in this issue of the Journal should leave you in no doubt that syphilis is back. After falling precipitously with the onset of the HIV epidemic in the early 1980s, syphilis infection rates are rising dramatically in Australia and the developed world among men who have sex with men.3 Why has this occurred, and what can be done about it? Australia’s response will determine if the current syphilis epidemic is remembered as an isolated epidemic or the return of endemic infection. The prevalence of a sexually transmitted infection (STI) is determined by three factors: the probability of transmission per partnership, the rate of partner change, and the duration of infectiousness. The particular importance of the duration of infectiousness is illustrated by the dramatic 100-fold fall in the prevalence of syphilis following the introduction of antibiotics.4 Another example is in situations where access to health care is poor and duration of infectiousness is therefore prolonged, as in isolated Indigenous communities in Australia. In such communities, both syphilis and gonorrhoea are common, despite rates of partner change being similar to those in the rest of Australia.5 In contrast, gonorrhoea or syphilis struggle to exist in communities with adequate access to health care, unless the rate of partner change is high. What then has changed among men who have sex with men to cause this sudden rise in syphilis infections in New South Wales and Victoria? Sexual behaviour has changed, with rates of any unprotected anal intercourse among men who have sex with men having increased by 50% in Australia over the last 10 years — this was also a strong risk factor for incident syphilis in the Health in Men (HIM) study6 mentioned in the research article by Jin et al.1 Oral sex is also transmitting syphilis, despite being considered relatively safe in terms of HIV transmission. Over half of the men in Jin et al’s cases series believed they had contracted syphilis through oral sex,1 and oral sex has been reported as the sole risk factor in up to 50% of cases reported overseas.3 HIV-positive men who have sex with men appear to be at increased risk of syphilis in Australia, representing between 40% and 54% of the cases reported by Jin et al1 and Guy et al.2 In addition, unprotected anal intercourse with an HIV-positive man was a strong risk factor for incident syphilis among HIV-negative men in the HIM Study.1 These findings are consistent with overseas reports that syphilis is more commonly diagnosed in HIV-positive men.3 The critical issue is what can be done now to control this epidemic. Clearly, increasing the use of condoms is important, particularly for anal sex. It is unlikely, however, that condoms will be widely used for oral sex, even though this practice is transmitting syphilis. In addition, reducing the rate of partner change is important, but it has been difficult to demonstrate large effect sizes in controlled studies.7 Substantially reducing the duration of infectiousness may be possible through educational campaigns, increased screening and enhanced contact tracing. Intensive educational campaigns for clinicians and men who have sex with men are fundamental for promoting early diagnosis and treatment, and screening high-risk individuals. Remember, most doctors under the age of 45 have not seen a case of syphilis, and young men are also less likely to be aware of the symptoms and clinical presentation of the infection. Educational campaigns that use the Internet can be relatively cheap and effective. For example, one banner advertisement on gay websites resulted in 32 270 click-throughs to public health websites with syphilis information.8 The cost per “click” varied from $0.05 to $10.8 Increased screening is the only way to detect asymptomatic infection; up to 33% of infections reported by Jin et al in the syphilis case series and the HIM study were asymptomatic.1 Guidelines suggest yearly testing for syphilis for any man who has had sex with another man in the past 12 months.9 This is easily justifiable given the syphilis incidence rate of 0.78 per 100 person years among men in the HIM study, but not necessarily easy to implement because it involves reaching all men who have sex with men, not just those attached to the gay community.1 Screening at every clinic visit for syphilis among HIV-positive homosexually active men may be necessary in view of the higher incidence of syphilis in this group. STI control is most cost effective if programs are focused on core group members who have large numbers of sexual partners. In the syphilis case series, up to two-thirds of the men had attended sex-on-premises venues or saunas where rates of STI infections have been previously reported to be extremely high.1,10 Contact tracing is an essential part of effective STI control but is difficult among men who have sex with men, whose partners are often anonymous. Nevertheless, innovative programs can prove effective. One study found that contact tracing was relatively effective even though the only identifying information available to public health officials were the “screen names” used in internet chat rooms. In this study, 41 of the 97 contacts of men infected with syphilis were traced through their “screen names”.8 Lastly, information about the epidemic, including the typical clinical features, who is affected, and risk factors for infection, is critical to inform intervention, as indeed both Jin et al1 and Guy et al2 have shown. For example, Jin et al provided much needed information about the usual clinical presentation of syphilis, finding that rash was the most common symptom (42%), but an ulcer or sore was also common (40%).1 As the rash of secondary syphilis is extremely infectious, identifying such cases early will significantly improve control. Australia’s response will determine if the current syphilis epidemic is remembered as an isolated epidemic or the return of endemic infection. Endemic syphilis will be expensive; both in human and financial costs, not least because it promotes HIV transmission. We need to learn from Australia’s effective and early response to the HIV epidemic that was characterised by community partnership, bipartisan government support, a commitment to harm minimisation and dynamic, original strategies.

Christopher K Fairley MB BS, PhD, FRACP · Jane S Hocking MPH, MHlthSc, PhD · Nicholas Medland MB BS

Objectives: To describe trends in the notification of infectious syphilis in New South Wales, the characteristics of homosexually active men recently notified with early syphilis, and the seroprevalence and incidence of syphilis, as well as associated risk factors, in a Sydney cohort of HIV-negative homosexually active men.Design, setting and participants: Secondary analysis of New South Wales infectious syphilis surveillance data from 1998 to 2003; a case series of 57 homosexually active men diagnosed with early syphilis in inner Sydney from December 2002 to January 2004; and a prospective cohort study of syphilis among 1333 HIV-negative homosexually active men in Sydney recruited from June 2001 to December 2003.Main outcome measures: Rates of notification of infectious syphilis in New South Wales and in areas of inner Sydney; behavioural and clinical features of men with syphilis in the case series; and incidence of syphilis and hazard ratios (HRs) associated with sexual behaviours in the cohort study.Results: Infectious syphilis notifications in inner Sydney rose more than 10-fold (from 6 in 1999 to 162 in 2003), and the increase was confined to men. Of 57 men with early syphilis in the case series, 54% were HIV-positive and 32% reported no symptoms of syphilis. These 57 men were highly sexually active and likely to report recreational drug use. In the cohort study, 1292 men (97% of participants) consented to syphilis testing; the incidence of syphilis was 0.78 per 100 person-years, and risk factors included reporting unprotected anal intercourse with HIV-positive partners (HR, 5.31; 95% CI, 2.00–184.93) and insertive oral sex (HR, 4.55; 95% CI, 1.14–18.18).Conclusion: Syphilis has been re-established among homosexually active men in Sydney, and HIV-positive men are over-represented. Frequent screening is needed in this population to curb the transmission of both syphilis and HIV.

Fengyi Jin MPH · Garrett P Prestage PhD · John M Kaldor PhD · Andrew E Grulich PhD, FAFPHM · Susan C Kippax PhD · Catherine M Pell MB BS · Basil J Donovan MD, FAChSHM

Rebecca J Guy,* David E Leslie,† Kleete Simpson,‡ Beth Hatch§ Jennie Leydon,¶ Margaret E Hellard,** Heath A Kelly†† * Epidemiologist, ** Head, Centre for Epidemiology and Population Health Research, Macfarlane Burnet Institute for Medical Research and Public Health, GPO Box 2284, Melbourne, VIC 3001; † Microbiologist, ¶ Senior Serologist, †† Head, Victorian Infectious Diseases Reference Laboratory, Melbourne, VIC; ‡ Surveillance Manager, § Partner Notification Officer, Blood Borne Viruses and Sexually Transmissible Infections Program, Department of Human Services, Melbourne, VIC. Rebecca. GuyATburnet.edu.au To the Editor: In Victoria, notifications of infectious syphilis infection (primary, secondary and early latent [< 2 years’ duration]), reported by the Department of Human Services, have increased more than fivefold in the past decade, from 16 in 1995 to 85 in 2004 (Box). An increase in notifications has also been observed in Sydney.1 Whereas previously in Victoria, very few infectious syphilis notifications were reported among men who have sex with men (1 of 16 cases in 1995), in 2004, 63 of a total of 85 cases (74%) were in this group (68% of these were acquired in Victoria). The Victorian Infectious Diseases Reference Laboratory (VIDRL) conducts testing for sexually transmitted infections (STI) and HIV for three Melbourne sexual health clinics with a high proportion of patients who are men who have sex with men. In 2004, 62 male patients tested positive for infectious syphilis, and 40% of these were HIV-positive. This is similar to the situation in Sydney, where in 2003, 54% of infectious syphilis cases were reported among HIV-positive men who have sex with men.1 Syphilis outbreaks among men who have sex with men have been reported elsewhere in recent years. There was an outbreak of syphilis in this group in Greater Manchester; between 1999 and 2002, and 37% of cases were in HIV-positive men.2 In this population, syphilis infection was associated with unprotected oral sex with high numbers of partners, seeking sexual partners at venues (darkrooms, cruising areas and saunas) and use of drugs (GHB [gamma hydroxybutyrate] and poppers [amyl nitrate]).3 A San Fransisco study in 2000, performed in response to a syphilis outbreak among men who have sex with men, reported that meeting sexual partners through use of the Internet was a factor significantly associated with syphilis infection.4 It is likely that some or all of the factors reported in these outbreaks overseas are contributing to the sustained increased in infectious syphilis notifications in Victoria, but it is important to have local data to ensure interventions are targeted appropriately and cost effectively. In Victoria, responses to the increase in syphilis notifications have already included an alert to general practitioners to encourage men who have sex with men to have syphilis testing and individual counselling, and syphilis testing of men who have sex with men at a popular sex-on-premises venue over a 4-week period. Depending on further studies in this population in Victoria, other responses could include enhancing outreach at Internet chat rooms, intensive counselling of HIV-positive men who have sex with men, and education interventions such as peer-led community-based strategies for countering unsafe sex and substance-use behaviours. Finally, it is vital that interventions are multidisciplinary, collaborative and evidence-based. Infectious syphilis notifications by year, Victoria Data from the Notifiable Infectious Diseases Surveillance System Database, Communicable Diseases Section, Victorian Department of Human Services.

Rebecca J Guy · David E Leslie · Kleete Simpson · Beth Hatch · Jennie Leydon · Margaret E Hellard · Heath A Kelly

To the Editor: Lymphogranuloma venereum (LGV) is an uncommon sexually transmitted infection caused by Chlamydia trachomatis serovars L1–3. LGV is not endemic in Australia, and rare Australian cases of LGV have been seen in patients who have either acquired the infection while travelling overseas in an endemic area, or have had local contact with an imported case. Currently, there is an outbreak of LGV in western Europe (in particular, The Netherlands) and the United States.1-4 A case of LGV in an Australian man with no history of overseas travel was managed recently. A 42-year-old bisexual man with previously treated early syphilis and hepatitis C infection presented to a Melbourne hospital in August 2004 complaining of 3 months of tender right inguinal lymphadenopathy. An excisional biopsy showed the formation of necrotising granuloma indicative of LGV. He had no history of penile ulceration, urethritis or proctitis. The surgical wound healed normally. The patient gave a history of attending sex-on-venue premises (“gay saunas”) and “beats”. He reported having oral sex with men, and recently having non-insertive sex involving masturbation with an unknown casual male contact who was apparently an overseas visitor. The patient had a female sexual partner with whom he had irregular, unprotected vaginal intercourse. The diagnosis of LGV was confirmed by polymerase chain reaction (PCR), which detected C. trachomatis, identified as serovar L2 by nucleotide sequencing, from the excised lymph gland. IgG and IgA antibodies to C. trachomatis were demonstrated by enzyme-immunoassay. Tests for other active sexually transmitted infections were negative. The patient was treated with doxycycline (100 mg twice daily for 3 weeks). His asymptomatic female partner was also treated. LGV is endemic in developing countries in our region, but occurs only sporadically in industrialised countries. The first stage of disease consists of a papule or ulcer that may occur on the penis, urethra or cervix. Proctocolitis may also be present, mimicking inflammatory bowel disease. Regional lymphadenopathy develops in the secondary stage of disease when there may be systemic symptoms. Fistula formation at these sites can be prevented by early recognition and treatment. Late, severe genital ulceration is rarely seen. Confirmation of a diagnosis of LGV requires showing C. trachomatis serovars L1–3 by serological tests or PCR on genitourinary specimens. Lymph node resection is not favoured because of the possibility of sinus formation. Prolonged treatment with doxycycline or roxithromycin for 3 weeks is required for affected patients. Asymptomatic contacts are treated with doxycycline for 1 week or a single dose of azithromycin. This case of locally acquired LGV highlights the features of this progressive disease that may now be recognised more frequently in Australian men who have sex with European or North American men. Histological section of the lymph node showing the thickened node capsule and necrotising granuloma Image courtesy of Dr Malcolm Buchanan, Department of Anatomical Pathology, Royal Melbourne Hospital.

Damon P Eisen

We know what to do, but doing it is the challenge In 1992, the late Fred Hollows warned of the catastrophic effects that HIV would have in remote Indigenous communities. His trademark candour caused considerable stir, and a number of important initiatives were implemented, such as the Tri-state HIV/STI Project in Central Australia and the National Indigenous Australians’ Sexual Health Strategy. However, it would be hard to argue that HIV is widely believed to be a priority in Indigenous health 13 years later. Health-seeking behaviour based on the presence of genital symptoms or awareness of risk is limited in many Indigenous communities . . . Until now, the prevalence of HIV in the Indigenous community has been considered similar to that in the non-Indigenous community.1 In this issue of the Journal (page 124), Wright et al present evidence of a higher rate of HIV among Indigenous people in Western Australia than in the non-Indigenous population.2 They report that, while the rate of HIV notifications in the non-Indigenous population declined between 1985 and 2002, it increased in the Indigenous population. The difference in risk for Indigenous women was striking — 39% of all female HIV notifications in WA since 1994 have been for Indigenous women, giving an Indigenous : non-Indigenous age-standardised rate ratio of 18. In contrast, the rate ratio for Indigenous males was 2. Wright et al also confirmed the marked differentials in risk of other sexually transmitted infections (STIs) in the Indigenous population — with Indigenous : non-Indigenous age-standardised rate ratios of 242 for syphilis, 77 for gonorrhoea and 16 for chlamydia. The data in this study are likely to predominantly reflect the situation in rural and remote regions of WA, and the authors acknowledge the difficulties of interpreting surveillance data. Nevertheless, the findings demand attention. Health-seeking behaviour based on the presence of genital symptoms or awareness of risk is limited in many Indigenous communities: the concept of “sexual health” is a construct usually confined to well-resourced urban populations. Few Indigenous children in remote areas complete high school and, as a result, there are few reliable means of informing young people about health risks. Although many Aboriginal Health Services have instituted local programs of distribution, condom use appears to be uncommon,3 and there is anecdotal evidence of an increase in injection drug use in remote areas. In settings of social disruption and dislocation, such as among individuals who congregate on the fringes of major urban areas, sex is often exchanged for favours, alcohol and other substances. Not surprisingly, reinforcement and maintenance of health messages and wide implementation of interventions are difficult to achieve in these settings. It is not entirely clear why the prevalence of HIV has remained low in remote Aboriginal Australia; however, this might be explained by the structure of local sexual networks. In simple terms, the sexual network identifies who is having sex with whom, how often and where. Individuals in a sexual network operate in a social space, not necessarily a geographic space. Because of the sensitivity surrounding this issue, there has been very little published on the complex sociocultural factors that determine the structure of Indigenous sexual networks in remote Australia. It is known that Indigenous people living in remote areas may travel extensively across the country, but are likely to choose partners they already know and who share the same background. This has been termed “assortative” partnering, and has been observed in other populations.4 The absence of HIV from a network protects all its members — it is only when an HIV-infected individual enters the network that transmission occurs. Such individuals may have travelled to large urban areas and contracted HIV through injection drug use or homosexual contact. As a result, a substantial proportion of the members of the sexual network will become infected, although in small communities the absolute numbers will remain low. This implies that control of HIV in the Indigenous population will require multiple small interventions that target individual sexual networks, as well as reflecting the local sociocultural conditions. In the 1990s, the rates of curable STIs (chlamydia, gonorrhoea and trichomoniasis) were found to be many times higher in the Indigenous population in the Northern Territory, compared with the non-Indigenous population. However, the rate of a non-curable, viral STI (human papillomavirus) was higher in the non-Indigenous than in the Indigenous population. This suggested that a major reason for the disparity in rates is the limited access to and use of clinical services in remote areas, rather than differences in average rates of partner change.5 Health professionals who have worked in remote health settings know how hard it is to do more than simply react to the patients who walk through the clinic doors with an acute problem. Maintaining population health programs, such as immunisation, health promotion and risk factor modification, is always difficult in these settings, and these programs are first to suffer when a medical crisis occurs. The opportunity costs of a local HIV epidemic are considerable: HIV does not just affect the individual who is infected — sexual partners are also at risk, and transmission can occur antenatally and during breastfeeding. Ongoing risk behaviour after a diagnosis of HIV is documented, driven by psychiatric and substance abuse-related factors. The medical system is compelled to react to the presence of HIV infection in a particular community. In one remote community, this required an increase in the staff of the local public health unit from three to eight, and other programs fell by the wayside (unpublished data). This migration of resources may be one of the major costs of an HIV epidemic in remote Indigenous Australia. Evidence from Africa suggests that STI control early in an HIV epidemic may be effective in limiting the spread of HIV,6 but this strategy is less useful once the HIV epidemic is established. Good STI control requires a coordinated program that addresses health promotion, diagnostic and screening services, rapid access to appropriate treatment and locally appropriate contact tracing. This is not easy, nor cheap, but it is possible — as seen with a successful program in Central Australia.7 Others have also implemented relatively effective programs.8 Primary care providers can use a new Medicare rebate item (item 710) to screen for STIs in Indigenous people as part of a broader preventive health assessment. The new National Aboriginal and Torres Strait Islander Sexual Health and Blood Borne Virus Strategy, to be announced later in the year, will provide a useful review of existing programs, and recommendations for specific action. HIV testing is central to HIV control: it determines the extent of the epidemic and helps plan local interventions. Antenatal screening and antiviral treatment of an HIV-infected mother can almost eliminate the risk of transmission of HIV to the neonate; appropriately timed therapy has obvious benefits for the individual in terms of morbidity and mortality, and successful treatment reduces the viral load and decreases the risk of transmitting HIV through sexual contact. There is no need to reinvent guidelines for testing in Indigenous settings — they already exist. Sustainable implementation is the challenge that faces primary care providers. The data from Wright et al provide a compelling reason for meeting this challenge now.

Francis J Bowden FRACP, MD

Objective: To compare trends and rates of HIV and sexually transmitted infections in Indigenous and non-Indigenous people of Western Australia.Design and setting: Analysis of WA notification data for chlamydia, gonorrhoea, and primary and secondary syphilis in 2002, and for HIV infections from 1983 to 2002.Main outcome measures: Rates of HIV and sexually transmitted infection by Indigenous status.Results: In 2002, there were 3046 notifications for chlamydia, 1380 for gonorrhoea and 64 for syphilis. When information on Indigenous status was available, Indigenous people accounted for 41% of chlamydia and 76% of gonorrhoea notifications, with Indigenous : non-Indigenous age-standardised rate ratios of 16 (95% CI, 14–17) and 77 (95% CI, 67–88), respectively. Indigenous people accounted for 90.6% of syphilis notifications (age-standardised Indigenous : non-Indigenous rate ratio, 242 [95% CI, 104–561]). From 1985 to 2002, HIV notification rates for non-Indigenous people in WA declined and rates for Indigenous people increased. From 1994 to 2002, there were 421 notifications of HIV infection in WA residents, 52 (12.4%) in Indigenous people and 369 (87.6%) in non-Indigenous people. Indigenous people accounted for 39% and 6.2% of all notifications in WA females and males, respectively. The Indigenous : non-Indigenous rate ratios were 18 (95% CI, 12–29) for females and 2 (95% CI, 1–3) for males.Conclusions: Indigenous Western Australians are at greater risk of HIV transmission than non-Indigenous people. Strategies to prevent further HIV infection in Indigenous Australians should include control of sexually transmitted infections.

Michael R Wright BSW, MAE(IH) · Carolien M Giele RN, BSc(Hons), MPH · Phyll R Dance BA, PhD · Sandra C Thompson FAFPHM, PhD

Macrophagic myofasciitis is characterised by sheets of macrophages in striated muscle, a few lymphocytes and inconspicuous muscle fibre damage. It is due to aluminium contained in vaccines, and is localised to the inoculation site. We report the first Australian case, detected incidentally when investigating a raised serum creatine kinase level. Clinical record During investigations for gastroesophageal reflux, a 32-year-old man was noted to have intermittently raised serum creatine kinase levels: 78 U/L in April 2003, 484 U/L in July 2003 and 8846 U/L in August 2003 (reference range, < 196 U/L), with normal troponin levels. He had no neuromuscular symptoms and played sport regularly. A previous serum creatine kinase level of 2000 U/L had been recorded in April 2000, when he had multiple pulmonary emboli after an overseas trip. He had been given inactivated hepatitis A (Havrix) and poliomyelitis vaccines intramuscularly in March 2000, and a booster inoculation for hepatitis A in February 2001. He was taking allopurinol for renal calculi and omeprazole for reflux. His father had died from motor neurone disease and a brother had fasciculations. The patient had no evidence of muscle weakness or wasting, no fasciculations, and the remainder of his neurological examination, as well as needle electromyography, was normal. Muscle biopsy The interstitial connective tissue of the deltoid muscle contained a dense infiltrate of large macrophages (Figure A). Electron microscopy showed spiculated structures within these macrophages (Figure B). When an electron beam hits a sample it releases x-rays of wavelength specific to the elements in the sample. Using this principle, an EDAX x-ray detector revealed an aluminium peak (Kα, 1.48 keV) from the aggregates. A: Deltoid muscle biopsy. Densely packed macrophages with abundant cytoplasm (arrowhead) were seen between muscle fibres (M), together with a few peripheral lymphocytes (thin arrow). No muscle fibre necrosis, regeneration, multinucleate giant cells, Michaelis–Guttmann bodies (found in malakoplakia) or granulomas were present. The macrophages stained positively with acid phosphatase and CD68. The lymphoid population showed a mixture of T and B lymphocytes. Stains for acid-fast bacilli were negative. (Haematoxylin and eosin. Bar = 50 m.) B: Electron micrograph showing electron-dense, randomly orientated, fine spiculated structures (asterisks) within a macrophage (M) (200 nm resin sections on nickel grids examined in a Philips CM120 electron microscope. Osmium and uranyl acetate. Bar = 1 µm.) Macrophagic myofasciitis is characterised by the presence of sheets of macrophages in striated muscle, a few lymphocytes and inconspicuous muscle fibre damage. It is due to the persistence of vaccine-derived aluminium in the muscle at the injection site and the myofasciitis is localised to the injection site. Since macrophagic myofasciitis was first described in 1993,1 more than 200 cases have been identified in France, with only a few cases reported from other countries.2 This is the first case of macrophagic myofasciitis reported in Australia. Aluminium is used as an adjuvant in diphtheria – tetanus –pertus sis, some Haemophilus influenzae type b, pneumococcal, hepatitis A and B, anthrax and rabies vaccines, as well as in tetanus toxoid.3 For example, each millilitre of Havrix contains 0.5 mg of aluminium, as aluminium hydroxide. The mechanism of macrophagic myofasciitis is thought to be secondary to an ongoing local immune reaction to the long-term persistence of this aluminium in the muscle.4 Macrophagic myofasciitis commonly occurs in adulthood, although the age ranges between 1 and 70 years.5,6 The clinical picture is variable, and includes nonspecific symptoms such as myalgia, arthralgia, muscle tenderness, muscle weakness, fever and fatigue. A few patients show raised serum creatine kinase levels and myopathic electromyography.6,7 Neurological manifestations resembling multiple sclerosis have been reported in some patients,8 and rarely it is associated with other diseases such as inclusion body myositis.9 Co-existent autoimmune diseases have been recorded in some patients with macrophagic myofasciitis.10 Steroids, analgesics and antibiotics have been used in attempts to treat this condition.10 Our patient did not have any neuromuscular symptoms and the muscle biopsy was performed because of his raised serum creatine kinase level. There was no correlation between macrophagic myofasciitis and the clinical signs and symptoms in this patient, who was asymptomatic. Therefore, we consider this histological finding to be incidental in a patient with a “CKopathy”. Recently, a genetic predisposition to macrophagic myofasciitis has been suggested to account for the disparity between the low prevalence of this disorder and the widespread use of aluminium-containing vaccines, as well as the variable incidence of this condition in different populations.5 The diagnosis of macrophagic myofasciitis is important to bear in mind, as other diagnoses such as sarcoidosis, connective tissue disease, tuberculosis, Whipple’s disease and malakoplakia may be entertained. The patient could then be subjected to needless further investigations and undue anxiety. We hope this report will help increase awareness of this condition, and predict that more Australian cases will come to light in future deltoid muscle biopsies.

Meena Shingde MB BS, MD · Roger Pamphlett MD, FRACP, FRCPath · James Hughes FRACP · Ross Boadle Dip(MT), MAIMS · Edward J Wills MD, FRCPA

Clinical record 1 Area of necrosis on right shin 2 Areas of necrosis at graft site A 50-year-old woman was referred for surgical consultation after accidental self-inoculation with Gudair ovine Johne’s disease (OJD) sheep vaccine 18 days earlier. The automatic vaccination syringe had been hanging from her neck by a plastic delivery tube connected to the vaccine pack when a sheep had bumped the syringe. This resulted in a needle-stick injury to her right shin. Within hours, the area became red, and 3 days later she consulted her general practitioner. Tetanus toxoid was administered, and she commenced a course of dicloxacillin. The inflammation failed to resolve and had progressed to a 2 cm-diameter area of skin necrosis by the time of presentation (Box 1). The necrotic skin and subcutaneous fat were then debrided. Despite careful wound packing, a tender nodule developed in the overhanging edge of the ulcer. On Day 15 after presentation, soft granulation tissue extending down to the deep fascia and the overhanging skin were debrided. A week later, a split skin graft was applied. Although the graft was successful when seen about 7 weeks after initial presentation, two red, tender areas had appeared about 5 mm from the edge of the graft. Within a further 9 days, the inferolateral area had proceeded to necrosis. At the patient’s request, further surgery was delayed until 2 months later (Box 2), when two necrotic areas and associated granulation tissue (arrows A and B) were curetted. No obviously oily material was detected (mineral oil is a component of the vaccine). The uppermost red tender area (arrow C), had settled, but subsequently flared up and discharged a little serous fluid. All three areas of necrosis had finally healed when the patient was seen 6 weeks later, and there was no evidence of inguinal lymphadenopathy, although the patient reported continuing fatigue and nausea. During the course of treatment of the leg, she developed recurrent urinary tract infections due to Proteus mirabilis. Histopathological observations on all occasions showed necrosis with adjacent marked oedema and granulation tissue, with polymorphs and occasional acid-fast bacilli (at the time of the first and second operation) but no microcavities suggestive of oil implantation. No stains are available to help differentiate human oil from mineral oil. No pathogens were cultured. For the past year, the patient has been free of systemic symptoms and her leg remains healed. Ovine Johne’s disease (OJD) is a chronic wasting disease of sheep caused by the “S” strain of Mycobacterium avium subsp. paratuberculosis. It has spread widely through Australian sheep flocks, causing significant economic loss since it was first detected in New South Wales in 1980. A national vaccination program to control OJD is currently in progress using Gudair vaccine (CZ Veterinaria, Porriño, Spain),1 which is distributed by Pfizer Animal Health. (The Gudair vaccine has been available in Australia since late 1999 for experimental use in about 50 approved flocks. This research work led to registration of the product in April 2002.) Vaccination of sheep against OJD is now widespread in Australia: over 7 million vaccinations have been performed — primarily in the central and southern tablelands and south-west slopes of New South Wales, across Victoria and on Kangaroo Island (SA), and to a lesser extent in the northern tablelands and western areas of NSW, mainland South Australia, Tasmania and Western Australia. Each 1 mL dose of Gudair contains killed (heat-inactivated) Mycobacterium paratuberculosis organisms and mineral oil, with thiomersal as a preservative. The oil forms a depot at the injection site to act as a potent adjuvant, stimulating a cell-mediated immune response to the mycobacteria. In humans, accidental injection or exposure of the skin surface or mucous membrane may cause a severe local reaction and, uncommonly, a systemic reaction. Despite education of vaccinators, there have recently been seven documented cases of accidental self-inoculation in Australia resulting in prolonged morbidity.2,3 Wider use of the vaccine has increased the risk of self-inoculation injuries. There is a need to improve safety for farmers during vaccination and to bring the potential for serious complications of self-inoculation to the attention of doctors in rural areas. Accidental self-injection may occur because of inadequate animal restraint, poor inoculation technique or carelessness, facilitated by hanging the automatic vaccinating syringe from the neck (Box 3) or shoulder.3 Although self-inoculation in this patient did not appear to penetrate the deep fascia, there was nonetheless severe long-term morbidity. The volume of injected material that is sufficient to cause necrosis is unknown. It is postulated that the adjuvant mineral oil combined with killed mycobacterial cell-wall components is responsible for provoking the necrotic response.3 This explains why antibiotics do not prevent necrosis and why surgical debridement of the inflammatory vaccine material is the preferred therapeutic approach. Mycobacterial cell-wall antigens have been traditionally added to oil-emulsion adjuvants (Freund’s complete adjuvant) to enhance the efficacy of experimental vaccines in stimulating cell-mediated immune responses. Such oil-based adjuvants, although generally considered too reactive for routine use in human vaccines, are considered acceptable for use in animals. Research in heavily OJD-infected Australian merino sheep flocks has shown that OJD vaccine injection-site lesions are common, but usually cause minimal untoward sequelae when administered subcutaneously at the recommended site (ie, high on the neck behind the ear).4 Necrosis similar to that seen in human case reports is usually only observed in a small proportion of vaccinated sheep. The vaccine product label clearly states that users should seek medical attention immediately if accidental self-administration occurs. Further information is contained in a fact sheet provided to farmers that emphasises the importance of avoiding exposure to the vaccine and outlines the procedure to follow if exposure occurs.5 A more detailed fact sheet prepared for medical practitioners, based on reports in the medical and veterinary literature,6,7 outlines a graded medical and surgical approach to intervention after clinical assessment of the patient’s condition.8 Box 4 presents a summary of our recommendations for treatment of accidental self-inoculation with OJD vaccine. These are based on the manufacturer’s recommendations, together with preliminary evidence from the case described here and a series of six similar cases.3 Accidental self-inoculation with Gudair vaccine has major occupational health and safety implications, and it is essential that medical practitioners be aware of the emerging use of oil-based OJD vaccine in the sheep industry and the potential seriousness of accidental self-inoculation. Further information is available from the Poisons Information Centre (tel: 13 11 26) or Pfizer Animal Health Veterinary Services (tel: 1800 814 883). Lessons from practice Accidental injection of the skin or exposure of the skin surface or a mucous membrane to an oil-based animal vaccine may cause a severe local, or occasionally systemic, reaction. Redness after exposure to vaccine material may indicate a granulomatous reaction with associated necrosis, rather than infection. Necrosis or apparent abscess requires early surgery to remove necrotic tissue and any remnants of the vaccine material. Despite debridement, prolonged morbidity may occur. 3 Administration of sheep vaccine for ovine Johne’s disease Note vaccine and syringe slung from neck. ◆ 4 Recommended treatment following accidental self-inoculation with ovine Johne’s disease vaccine Category 1 injury (superficial skin exposure). Simply wash the contaminated area. If vaccine material is splashed onto mucosal surfaces (eg, eyes), there is greater risk of a local adverse reaction, and topical corticosteroids should be considered. Category 2 injury (simple needle-stick injuries without injection). Treat symptomatically (eg, wash skin, ensure appropriate tetanus cover, prescribe topical corticosteroids and oral antibiotics to prevent opportunistic infection). Category 3 injury (injection of vaccine material). Acute pain and inflammation are usually evident within 24 hours. Perform early surgery and drainage to remove the oil-based vaccine material before it spreads or elicits a severe granulomatous reaction. Category 4 injury (lesion that has progressed to necrosis or granulomatous ulceration). Perform surgical debridement to remove any residual vaccine material. Skin grafting may ultimately be required.

Graeme D Richardson MB BS, FRACS, FRCS · Ian I Links BVSc, DipBact · Peter A Windsor BVSc, PhD

A dengue fever epidemic was recognised in the Torres Strait Islands of Queensland in late 2003. Two fatal cases of dengue haemorrhagic fever occurred in early 2004. This severe manifestation is more common when a patient is infected a second time, with a different virus serotype to the first infection. These are the first fatalities related to dengue fever in Australia in over a century. Clinical recordsPatient 1A 40-year-old woman from Thursday Island in the Torres Strait, north Queensland (Box 1), presented to a local hospital in February 2004 with a 6-day history of feeling generally unwell, plus generalised body aches and fevers, and 3 days of vomiting and diarrhoea. She had type 2 diabetes and was taking metformin. She had been seen at a primary health care clinic on Days 2 and 5 of the illness and was diagnosed clinically with dengue fever based on the typical symptoms, as this infection was epidemic at the location. Blood samples were taken on both occasions. On admission to hospital, she was delirious and restless, with a pulse rate of 120 beats/min and blood pressure of 100 mmHg systolic by palpation only. Petechiae were noted around the right elbow. She was given 2 L of intravenous fluid. Six hours after admission, she became more agitated and restless, with blood pressure of 123/55 mmHg and pulse rate of 150 beats/min. She was given a small dose of morphine. Thirty minutes later, her blood pressure became unrecordable. Despite 5 L of intravenous fluids over the next 7 hours, together with adrenaline and metaraminol, the blood pressure remained very low. A single dose of ceftriaxone (2 g) was given, and evacuation to a referral hospital was arranged. The retrieval team noted that the patient’s skin was cold and clammy and recorded a blood pressure of 90/55 mmHg. The pulse rate fell, and blood pressure became unrecordable before arrival at the referral hospital, and she could not be resuscitated. An autopsy was not performed. Between Days 2 and 6 of the illness, the patient’s haematocrit rose from 0.42 to 0.55 (reference range [RR], 0.36–0.52), and her platelet count fell from 144 × 109/L to 4 × 109/L (RR, 150–400 × 109/L). There was a moderate increase in hepatic enzyme levels: aspartate aminotransferase (AST), 1270 U/L; and alanine aminotransferase (ALT), 310 U/L (RR, < 40 U/L for both). Dengue virus type 2 was detected by both reverse transcriptase polymerase chain reaction (RT-PCR) testing and viral culture. Previous tests for dengue antibody, in 1998, were positive for IgG. The pattern of antibody response during the current illness was that of secondary infection. Culture of blood taken at the time of admission to the local hospital grew Escherichia coli. A diagnosis of dengue haemorrhagic fever was made, based on World Health Organization criteria1 (Box 2). Patient 2In March 2004, a 70-year-old man from an island north of Thursday Island had a 1-day history of dyspnoea, cough and a low-grade fever. He had type 2 diabetes, raised cholesterol level and hypertension. His wife called the local medical clinic during the night as he was agitated and semiconscious. His blood sugar level was noted to be low. Glucagon was administered on the advice of medical staff on Thursday Island, and his mental state improved slightly. His blood pressure was 80/60 mmHg. The patient was evacuated to Thursday Island the following day. On arrival, his temperature was 37.1°C, pulse rate was 93 beats/min, and blood pressure was 120/70 mmHg. His respiratory rate was 28 breaths per minute, oxygen saturation was 93% breathing room air, and he had several episodes of diarrhoea. He was given 2 L of intravenous fluid. He continued to complain of dyspnoea, and a chest x-ray showed hyperinflated lungs. A provisional diagnosis was made of an acute exacerbation of airways disease, and treatment was begun with prednisolone (50 mg per day). His blood pressure remained low (90–100 mmHg systolic). Thrombocytopenia (11 × 109 cells/L) was noted on a blood film, and the possibility of dengue fever was raised, although the infection was not then known to have spread to the patient’s home island. Hepatic enzyme levels were mildly elevated (AST, 126 U/L; ALT, 99 U/L). The following day, the patient had a sudden large melaena and became hypotensive. This was followed by bradycardia and cardiac arrest. He was resuscitated, intubated and ventilated, and then evacuated to a referral hospital. He received a blood transfusion but had further melaena, and was dependent on inotropic support in the intensive care unit. Blood was noted in his stomach after insertion of a nasogastric tube. Despite receiving antibiotics for presumed sepsis, he died later the same day. An autopsy was not performed. A retrospective diagnosis was made of probable dengue haemorrhagic fever. Dengue virus type 2 was cultured from blood taken on Day 4 of the illness. Dengue IgG, but not IgM, antibodies were detected in serum taken on Day 2, consistent with a secondary dengue infection. There was a fall in haematocrit from 0.48 to 0.39 between Days 4 and 5 of the illness. A chest x-ray done in the intensive care unit showed a right upper lobe infiltrate, but no evidence of pleural effusions. DiscussionThese two cases are, to my knowledge, the first fatalities related to dengue fever in Australia in over a century. Previous fatalities were described during a large epidemic of dengue fever in Charters Towers (north Queensland) in 1897.2 Dengue fever is caused by infection with one of four serotypes of dengue virus and is transmitted from human to human through the bite of the mosquito vector Aedes aegypti. Clinically, the infection is characterised by a febrile illness associated with generalised body aches, and occasional minor bleeding manifestations. A more severe form of the disease, dengue haemorrhagic fever, has become an increasing cause of morbidity and mortality throughout the tropical world. There are an estimated 50–100 million cases of dengue infection each year, including about half a million cases of dengue haemorrhagic fever. The number of cases of both dengue fever and dengue haemorrhagic fever has increased dramatically over the past few decades, and the geographical range has extended to involve most tropical countries.3 The frequency of dengue haemorrhagic fever is much greater during secondary dengue infections than during primary infection. As immunity to infection with the same dengue serotype is probably lifelong, secondary infections are usually caused by a different virus serotype. Antibodies raised in the initial dengue infection may cause an immune enhancement in a subsequent infection with a different dengue serotype.4 Epidemics of dengue haemorrhagic fever can occur when a particular population is subject to sequential epidemics caused by different serotypes.5 Cases of dengue haemorrhagic fever, including some fatal cases, were first described in Australia during the 1897 epidemic in Charters Towers.2 This followed another large epidemic in the town in 1894–1895. As individuals were described with symptoms during both epidemics, they were probably caused by different serotypes. A large epidemic of dengue fever in Townsville and Charters Towers in 1992–1993 raised the possibility of the re-emergence of dengue haemorrhagic fever in Australia.6 These fears have been repeated with each subsequent epidemic.7 Diagnosis of dengue haemorrhagic fever is based on clinical and laboratory findings (Box 2), and severity is graded 1 to 4.1 Grade 3 is defined as circulatory failure manifested by rapid and weak pulse, and narrowing of pulse pressure (20 mmHg or less) or hypotension, with the presence of cold clammy skin and restlessness. Grade 4 is defined as profound shock with undetectable blood pressure and pulse. Grades 3 and 4 dengue haemorrhagic fever are termed dengue shock syndrome.1 Both Patient 1 and Patient 2 were classified with grade 4 dengue haemorrhagic fever. Patient 1 had skin petechiae, haemoconcentration, thrombocytopenia, and fever. The presence of E. coli in the blood may have contributed to her death, but the pattern of illness was otherwise typical of dengue haemorrhagic fever. She was treated with an antibiotic with activity against E. coli. Concurrent bacterial infection may occur in dengue haemorrhagic fever and is more common in older patients.8 The death generated considerable publicity and has heightened awareness of the condition among clinical staff in the Torres Strait Islands. Patient 2 had a fall in haematocrit of about 20% between Days 4 and 5 of the illness, but evaluation of the degree of haemoconcentration was complicated by haemorrhage and transfusion. Although a chest x-ray did not demonstrate pleural effusion (which would have provided evidence of vascular permeability), the clinical endpoint of vascular permeability — hypotension and shock — was certainly evident. Both patients had evidence of recent infection with dengue virus type 2. A dengue 2 epidemic was recognised in the Torres Strait Islands in late 2003, following the admission of two patients (aged 32 and 42 years, respectively) to the intensive care unit at Cairns Base Hospital with severe hepatitis. Both these patients fulfilled the clinical criteria for dengue haemorrhagic fever and had serological evidence of secondary dengue infection. From November 2003 to April 2004, there were 176 laboratory-confirmed cases of dengue fever in the Torres Strait, mostly on Yam Island and Thursday Island (Alyssa Pyke, Queensland Health Scientific Services, personal communication). Smaller epidemics, also caused by dengue virus type 2, occurred concurrently in Cairns and Townsville. Previous epidemics of dengue fever in the Torres Strait Islands occurred in 1996 (dengue 2) and 1981 (dengue 1).9 The latter was the only non-dengue 2 epidemic that has been well documented in the Torres Strait Islands.10 The most plausible scenario in the four cases of dengue haemorrhagic fever in 2003–2004 is that primary infection occurred in 1981. This implies that secondary infection more than 20 years after primary infection may still produce severe manifestations. The same observation was made after an epidemic of dengue 2 in Cuba, 20 years after a dengue 1 epidemic.11 The patients with dengue haemorrhagic fever described here were aged 32 to 70 years. In contrast, in south-east Asia, dengue haemorrhagic fever is predominantly a paediatric condition. A possible explanation for the older age of the Queensland patients is that the interval between the dengue 1 and dengue 2 epidemics meant that only older people had dengue 1 antibodies. Epidemics of dengue fever appear to have become more frequent in north Queensland, with five major epidemics (three affecting the Torres Strait) and many smaller epidemics between 1992 and 2004. Control measures instituted by public health authorities may have averted more frequent larger epidemics.12 In contrast, the previous five major epidemics occurred over a period of 90 years. Increasing international travel into north Queensland and global increase in dengue activity will inevitably lead to further introductions of the virus into north Queensland. Indeed, another outbreak — of dengue type 4 — was declared in the Torres Strait in March of this year.13 Aggressive case-finding and mosquito control are our major defences against further epidemics and the attendant risk of dengue haemorrhagic fever. The major clinical feature of dengue haemorrhagic fever is intravascular fluid loss. Expert clinical management of dengue haemorrhagic fever with aggressive intravenous fluid replacement has reduced the mortality rate to less than 1% in centres experienced in fluid resuscitation.14 This compares with mortality rates up to 30% in some series.3 Medical staff in high-risk areas are now alert to the possible future occurrence of this syndrome. 1 Location of the Torres Strait Islands The Torres Strait Islands lie between mainland Papua New Guinea and the tip of Cape York in Australia. The two major foci of the dengue epidemic were Yam Island and Thursday Island. 2 Diagnostic criteria for dengue haemorrhagic fever (World Health Organization)1 Clinical findings Fever lasting 2–7 days; and Haemorrhagic manifestations, ranging in severity from a positive tourniquet test through to clinically obvious bleeding. Laboratory findings Platelet count < 100 × 109 cells/L; and Haemoconcentration, as evidenced by a 20% rise in haematocrit (or a 20% fall after rehydration).

William J H McBride FRACP, FRCPA, PhD

Ashwin Swaminathan,* Iain B Gosbell,† Nicholas A Zwar,‡Mark W Douglas§ * Infectious Diseases Registrar, † Director and Associate Professor, § Infectious Diseases Physician, Department of Microbiology and Infectious Diseases, Liverpool Hospital, South Western Area Pathology Service, Locked Bag 7090, Liverpool, NSW 1871; ‡ Director and Professor of General Practice, Sydney South West Area Health Service General Practice Unit, Fairfield Hospital, Sydney, NSW. Iain. GosbellATswsahs.nsw.gov.au To the Editor: Infestation with the sandflea Tunga penetrans, or “chigoe flea”, is rarely encountered in Australia, but has been noted in children recently arrived from Central–East Africa. There have been only two previous Australian case reports of this parasitic infection, both in adult travellers returning from Africa.1,2 Several families who had been living in crowded refugee camps in Tanzania underwent routine screening for infection within 2 weeks of arrival in Australia. Four of 14 children examined had cutaneous lesions on their feet — mainly on the toes, nail beds and interdigital spaces (Box). These lesions were papular, less than 1 cm in diameter, pale yellow with dark centres, and were variably painful and/or itchy. Chronic, adjacent skin and nail bed changes were evident, as were small, loosely attached seed-like objects. Papules could be lifted with a sterile needle, leaving a small, non-bleeding cavity. Tunga penetrans, with numerous attached eggs, was identified by microscopy. Tungiasis occurs when an impregnated female sandflea burrows into the unprotected skin of a warm-blooded host. There is a predilection for the feet, although the perineum, buttocks and arms may also be infected.3 The head of the sandflea breaches the upper dermis to feed on blood vessels, while the abdomen traverses the epidermis, with its posterior components (anus, genital opening and respiratory spiracle) reaching the surface, forming a papule. Over several weeks, the flea releases hundreds of eggs before dying. After hatching, the larvae thrive in dust, soil and sand; they are found on beaches and in animal stockyards of tropical countries.3,4 Infection of pigs and other livestock, the usual host reservoirs, has led to significant problems in the livestock industry.1,4 Apart from pruritis and pain caused by local inflammation, morbidity results from ulceration and secondary bacterial infection, including tetanus and gas gangrene.1,2,4 Fleas can be removed using a sterile needle and forceps, and secondary complications prevented with tetanus prophylaxis, and antibiotics as appropriate. Successful outcomes with antiparasitic agents, such as ivermectin and thiabendazole, have also been recently reported.5 Tungiasis is indigenous to Latin America and the Caribbean, but was introduced to Africa, where it is now endemic, and to parts of South Asia.4 Given the current influx of African refugees into Australia, including the tropical north, the obvious concern is whether Tunga penetrans could establish itself here. We encourage medical practitioners dealing with newly arrived African refugees to examine for tungiasis in their screening evaluation. If, as suspected, this condition is prevalent, national infection control guidelines aimed at preventing establishment of the disease in Australia may be needed. Lesions caused by Tunga penetrans, the “chigoe” sandflea A characteristic Tunga penetrans lesion (thick arrow), with pale-yellow papule and dark centre, and a less obvious lesion (thin arrow) with surrounding chronic skin changes and multiple, loosely attached eggs.

Ashwin Swaminathan · Iain B Gosbell · Nicholas A Zwar · Mark W Douglas

Objective: To evaluate the effectiveness of a community-based and GP-based intervention in reducing unnecessary antibiotic prescribing for upper respiratory tract infections (URTIs) including sore throats, sinusitis and otitis media.Design: Analysis of pharmacy dispensing data in June to October before (2000) and after (2001) the intervention, which commenced on 25 June 2001.Setting and participants: Local consumers, health professionals, the Adelaide Southern Division of General Practice, the South Australian Government, and the local media in a rural region of South Australia, covering about 2000 square kilometres, with a population of over 20 000.Intervention: Community dissemination of consumer information on antibiotic use for URTIs (including a local media campaign) and education of health professionals (including sessions with general practitioners at the four practices in the study area) on current Australian therapeutic guidelines for antibiotics, and a validated clinical scoring system for decision making in managing sore throat.Main outcome measures: Total dispensing data from local pharmacies for the months of June to October in 2000 and 2001, covering the six antibiotics considered most likely to be used for URTIs (amoxycillin, amoxycillin/clavulanic acid, cefaclor, doxycycline, erythromycin and roxithromycin).Results: The dispensing of the six antibiotics reduced by 32% overall, from 77.1 to 52.9 defined daily doses per 1000 population per day, with statistically significant reductions in the range of 31%–70% for individual antibiotics; there was no reduction for amoxycillin with or without clavulanic acid.Conclusion: The intervention was associated with reduced dispensing of unnecessary antibiotics for URTIs.

William B Dollman BPharm, MAppSc, FSHP · Vanessa T LeBlanc BA(Psych) · Lynette Stevens · Peter J O’Connor PhD · John D Turnidge MB BS, FRACP, FRCPA

Christopher M MacIsaac,* Mark A Page,† Beverley-Ann Biggs,‡ Kumar Visvanathan§ * Associate Intensivist, † Registrar, ‡ Associate Professor, The Royal Melbourne Hospital, Grattan Street, Melbourne, VIC 3050; § Senior Research Fellow, Murdoch Children’s Research Institute, Melbourne, VIC. Christopher.macisaacATmh.org.au To the Editor: We report a recent case of toxic shock syndrome associated with menstruation which illustrates that this syndrome still occurs, even when tampons are used appropriately. A potential diagnostic test for the syndrome is also discussed. An 18-year-old woman presented with a 1-day history of fever, chills and severe back pain, with no other focal symptoms. On examination, she was febrile with a blood pressure of 75/40 mmHg, and had begun vomiting. She was treated empirically with intravenous ceftriaxone and flucloxacillin and resuscitated with intravenous fluids. Over several hours, the back pain resolved, and a widespread erythrodermic rash developed, centred mainly on the trunk. Further questioning revealed that the patient had removed a tampon shortly before presentation, as she had just ceased menstruating. Renal ultrasound examination, chest x-ray and blood cultures were non-diagnostic. She was treated with intravenous antibiotics for 4 days and discharged home with a further 10-day course of oral amoxycillin and clavulanic acid. At outpatient follow-up 3 weeks after admission, she reported desquamation of the skin of her palms and soles. Toxic shock syndrome was first described in 1978,1 and a strong association with Staphylococcus aureus, menstruation and tampon use was established in 1980.2 Toxic shock syndrome toxin-1 (TSST-1), a protein secreted by S. aureus, was the first of many toxins associated with the syndrome to be identified. The term “superantigen” was adopted to describe the ability of these toxins to cause a remarkable expansion of T lymphocytes displaying specific β chain variable regions of the T-cell antigen receptor. Superantigens bypass normal antigen presentation and can stimulate over 20% of all T cells, whereas a conventional antigen stimulates only in the order of 1 in 10 000 T cells. The signature feature of superantigen activity is the expansion of lymphocyte populations bearing the particular Vβ chains that bind the superantigen. In the case of TSST-1, this is Vβ2.3 Our patient consented to blood being sampled to investigate the Vβ profile of her T cells at follow-up. This investigation was part of a broader study on superantigens in sepsis that was approved by the Ethics Committee of the Royal Melbourne Hospital. The blood was stained with monoclonal antibodies against 24 Vβ families4 and analysed by flow cytometry. This showed a massive expansion of Vβ2 cells, which accounted for 28% of all CD4 lymphocytes (Box). Currently, there is no diagnostic test for toxic shock syndrome. Toxin production from cultured organisms can be established in vitro by some laboratories, but does not confirm toxin production in vivo. Detection of a “skewed” Vβ repertoire is a potential diagnostic test. Clearly, the sensitivity and specificity of the assay would need to be established before general application. To date, we have found skewed Vβ T-cell profiles in six independent cases of toxic shock syndrome. This patient had used tampons appropriately, including replacing tampons at least every 4 hours and not using them overnight, but nevertheless developed a life-threatening disease. The incidence of toxic shock syndrome peaked in the United States in 1980 and has since fallen substantially, as a result of factors including changed tampon absorbency. However, the incidence may be now increasing.5 Our case serves to remind us all to be vigilant for toxic shock syndrome in association with menstruation, and to consider the diagnosis in all patients with severe sepsis. Vβ profile of the T-cell antigen receptor of CD4 lymphocytes in a patient with toxic shock syndrome Vβ profile of CD4 cells from a patient 21 days after onset of toxic shock syndrome compared with the mean profile from 11 adult intensive-care patients with no evidence of infection. Note the massive expansion of cells carrying Vβ 2, for which toxic shock syndrome toxin-1 has known affinity.

Christopher M MacIsaac · Mark A Page · Beverley-Ann Biggs · Kumar Visvanathan

Patrick M Schlievert Professor, Microbiology, University of Minnesota, 420 Delaware Street SE, Minneapolis, Minnesota 55455, USA. patsATlenti.med.umn.edu Comment: As noted by MacIsaac et al above, my colleagues and I recently reported an increase in the incidence of staphylococcal toxic shock syndrome (TSS) in Minneapolis–St Paul in the United States, from 0.8 per 100 000 (in January 2000) to 3.4 per 100 000 (in December 2003).1 We noted that physicians across the United States were reporting TSS cases in increasing frequency. There are two major categories of staphylococcal TSS, menstrual and non-menstrual.2,3 Menstrual TSS is defined as occurring during menstruation or within the 2 days preceding its onset or the 2 days following its cessation; the illness is primarily, but not exclusively, associated with tampon use. Menstrual TSS is nearly always caused by the superantigen exotoxin, TSS toxin-1 (TSST-1).4 Superantigens significantly overactivate the human immune system to release cytokines that cause the clinical features of TSS (interleukin-1β [endogenous pyrogen]; tumor necrosis factor-α and β [capillary leak]; and interferon-γ and interleukin-2 [rash]).5 Non-menstrual TSS may occur in anyone, young or old, male or female, and today commonly follows superinfection of the upper respiratory tract after viral infection. Non-menstrual TSS is caused by TSST-1 (50%) or by staphylococcal enterotoxin B or C (together nearly 50%). The important question is what accounts for the fourfold rise in TSS that was reported in our 2004 study? We proposed several hypotheses. First, the increase in incidence partly results from the emergence of three strains of methicillin-resistant Staphylococcus aureus (MRSA), at least two of which are emerging worldwide. These strains are termed (by Centers for Disease Control [CDC] nomenclature) USA 1100 (TSST-1 positive), USA 400 (SEB/SEC, Panton–Valentine leukocidin [PVL] positive), and USA 300 (positive for an unknown superantigen as well as PVL). In our studies, USA 1100 strains currently comprise 20% of submitted isolates, compared with none before the year 2000. These isolates may produce 10 to 100 times more TSST-1 in vitro than their methicillin-sensitive S. aureus counterparts matched by pulsed-field gel electrophoresis profile. Thus, these organisms rapidly produce high levels of TSST-1, leading to TSS even when lower-absorbency tampons are used. In addition, the USA 400 and USA 300 strains are also emerging and are associated with increases in non-menstrual TSS. These latter isolates also produce more superantigens than their methicillin-susceptible counterparts. Secondly, in our 2004 study, physicians who submitted cultures to our laboratory defined cases of TSS based on patient presentation and the presence of an S. aureus strain producing one of the three causative exotoxins. Our TSS definition is likely to be broader than the strict CDC definition. Finally, we also noted that it is possible that women are beginning to menstruate and to use tampons at earlier ages. In addition, teenagers are bombarded with media advice that TSS is no longer a problem; failure to recognise the illness may lead to it becoming more severe before presentation. These lifestyle and awareness changes, combined with the emergence of high-toxin-producing strains and the expanded definition of TSS, may account for the observed increase in TSS. The increase does not appear to be caused by changes in tampon composition or absorbency.

Patrick M Schlievert

Tulsi Menon Resident Medical Officer, Department of Orthopaedic Surgery, Royal Perth Hospital, 19 Morgan Road, Redcliffe, WA 6104 kaltulAToptusnet.com.au To the Editor: I report an infection with Dracunculus medinensis diagnosed incidentally on x-ray. The patient was a Sudanese immigrant, who had sustained a left knee joint effusion after falling. During management at Royal Perth Hospital, a calcified lesion with a serpentine appearance was seen on x-ray within soft tissues near the left knee joint. Its characteristic appearance, combined with the patient’s background, led to a diagnosis of D. medinensis (known as guinea-worm), a nematode parasite which causes dracunculiasis. The patient’s knee effusion was managed conservatively and improved within a few weeks. The effusion was secondary to the fall and believed to be unrelated to the calcified D. medinensis. Transmission of dracunculiasis is through consumption of contaminated water. The guinea-worm larvae mature and migrate towards the skin surface over 1 year (during which the patient remains asymptomatic), with over 90% of the worms appearing from the lower limbs. When in contact with water, the exposed guinea-worm releases larvae, and the lifecycle is completed when people ingest contaminated water.1 If the guinea-worms die before maturation, they usually calcify. The Global Dracunculiasis Eradication Campaign was established in 1981 with the aim of eliminating dracunculiasis through water sanitation efforts.1 With no vaccine or treatment, prevention is the only method of eliminating dracunculiasis. Since the campaign was established, the number of people affected by dracunculiasis has decreased by 98%. Currently, Sudan alone accounts for 73% of cases.1 Our patient migrated to Australia as a refugee from Sudan during the civil war. Her village in Sudan had only one source of water used for daily activities, including drinking. The patient knew many people with dracunculiasis, but did not know she had been infected. When calcified guinea-worms are discovered during routine radiological examination, they usually do not need treatment. Many people are not aware they have been infected. Muller reported 89% of patients with calcified guinea-worms were asymptomatic.2 No known previous case of a radiologically diagnosed calcified guinea-worm has been reported in Australia. The consequences of war and famine, with a resultant increase in refugees and immigrants from affected nations, is likely to increase the number of incidental calcified guinea-worms found in non-endemic countries. This disease may have a significant impact if affected immigrants arrive during the incubation period (when asymptomatic) and the parasite emerges from the skin after immigration (rather than calcifying), similar to the patient described by Spring.3 Thus, it is important for health personnel to be aware of dracunculiasis, including its radiological manifestations. Lateral view of left knee joint and distal left thigh A calcified lesion, representing Dracunculus medinensis within the soft tissues, is visible posterior and lateral to the distal femur near the knee joint. The calcification has a serpentine appearance: the proximal part coiled in appearance, the middle having a string-like linear appearance, and the distal part having dense curvilinear opacity.

Tulsi Menon

Questions of cost-effectiveness, vaccine efficacy and feasibility are yet to be answered In the United States, routine immunisation of all healthy children aged 6–23 months against influenza has recently been introduced. The principal justification for this is the relatively high morbidity and mortality from this disease in very young children.1 The United States is also considering routine influenza immunisation of all children aged over 6 months, in view of the herd protection it would provide to the adult population. Currently, Australian guidelines recommend immunisation of children in groups considered at high risk of severe influenza.2 Should Australia introduce universal childhood immunisation? There is no doubt that children have an extremely high incidence of influenza. It is estimated that, on average, 20%–43% of children are infected during typical influenza seasons.3-5 The incidence is highest in young children less than 2 years old, who are often hospitalised.1,3-5 The mortality due to influenza in infancy is second only to that in the most elderly patients.1 In the severe 2003–04 influenza season, 143 children died from influenza in the United States, of whom 58 (41%) were less than 2 years old and 65 (45%) had no underlying condition.1 These data emphasise the importance of protecting children with annual influenza immunisation, if feasible. Another reason to consider universal childhood influenza immunisation is herd protection. In what turned out to be an illuminating natural experiment, 50%–85% of Japanese schoolchildren were immunised annually against influenza from 1962 to 1987, but there was no routine immunisation of the elderly. When mandatory immunisation of schoolchildren was relaxed in 1987 and repealed in 1994 (because of doubts about safety and effectiveness), influenza immunisation rates dropped to very low levels. A retrospective study comparing excess mortality from pneumonia and influenza in Japan and the United States concluded that the vaccination of Japanese schoolchildren prevented about 37 000 to 49 000 deaths per year, mostly of elderly people. (This represented about one death for every 420 children vaccinated.)6 In considering the feasibility of universal childhood vaccination, vaccine efficacy is one of the factors that needs to be taken into account. In healthy adults under 65 years of age, inactivated influenza vaccine is 70%–90% effective when the match between vaccine and circulating viruses is close.1 However, the same vaccine may be less immunogenic in children. Studies in children aged 6 months to 15 years show a vaccine efficacy of 31%–91% against influenza A and 45% against influenza B.7,8 However, very few of the studies have examined children aged 6–23 months,9,10 the age group currently recommended for routine influenza vaccination in the United States. An alternative form of vaccine administration is on the horizon — live attenuated influenza vaccines. A recent systematic review10 suggested that live vaccines may be more effective than inactivated vaccines in children over 2 years of age (79% versus 65%). Live attenuated influenza vaccines have been licensed in the United States, and might be more acceptable because they are given intranasally.11 However, live vaccines cost a lot more and are not licensed for use in children under 5 years in the United States (because of limited safety data). They are not yet licensed in Australia for use in any age group. The high morbidity of influenza in children and the likely benefits due to herd immunity do make annual childhood influenza immunisation appear economically attractive. However, against this must be weighed the need to immunise with a new influenza vaccine each year, because of antigenic drift in influenza strains, and the need to give two doses of vaccine to children under 9 years in the first year they are immunised.1,2 In addition, the severity of influenza seasons varies unpredictably from mild to severe, and it costs as much to immunise in a mild year as in a severe one. In the United States, indirect costs (mainly days of work lost by parents) dominate economic analyses supporting the use of influenza vaccines in children.12 In Australia, by contrast, the Pharmaceutical Benefits Advisory Committee considers only direct costs of illness, so it is unlikely that a universal, publicly funded childhood immunisation program could be justified using such cost-effectiveness criteria. There may also be practical problems with attempts to introduce routine childhood immunisation. In 2004–05, the uptake of influenza vaccine for children aged 6–23 months in the United States, when the vaccine was recommended universally, was estimated to be only 48%.13 In Ontario, Canada, where all residents aged over 6 months have been offered free annual influenza immunisation since 2000,14 the 2003 uptake in children was only 27%.15 Parents of unimmunised children were more likely to believe that immunisation resulted in a flu-like illness, caused adverse effects more severe than the disease, or weakened the immune system.15 Such immunisation myths are common, although studies have repeatedly shown inactivated influenza vaccine align="right" to be safe, with low rates of adverse events and the benefits clearly outweighing the risks.1,2,9 Another practical issue is the question of how to fit the vaccine into an already crowded childhood vaccination schedule. In general, annual immunisation against influenza is recommended in autumn at the start of the influenza season; there is no fixed age of administration of vaccine. Implementing universal influenza vaccination would place a substantial extra burden on primary care practices.16 Considering all the available information, I believe that there is currently insufficient reason for introducing universal childhood vaccination for this disease in Australia. There are too many unanswered questions about the cost-effectiveness, efficacy and feasibility of universal immunisation of healthy children, whether infants or school-aged. For the time being, we should maintain a watching brief. Future data emanating from Ontario and the United States may provide us with a clearer answer as to whether large-scale programs of routine childhood influenza immunisation are feasible and effective. Further, if the US experience with live vaccines shows consistent immunogenicity and improved ease and acceptability of administration, live vaccines may yet prove to be a cost-effective way to implement universal childhood influenza immunisation in Australia. One thing is clear: influenza vaccination is most cost-effective for children considered at high risk of severe influenza, such as those with chronic cardiopulmonary and other chronic illness. These children should clearly be vaccinated annually against influenza.1,2 Yet vaccine coverage of high-risk groups aged 2–17 years is only 35% in the United States,13 and probably lower in Australia, although we lack age-specific data. Australian immunisation providers should redouble their efforts to ensure that children at high risk are immunised annually.2 Also, it should be remembered that the Australian immunisation handbook2 does not preclude vaccinating others who are not at high risk. It states that “influenza vaccine should be administered to any person who wishes to reduce the likelihood of becoming ill”.

David Isaacs MD, FRACP, FRCPCH

We report on an elderly couple who presented with a syndrome that included severe generalised tremor and incoordination after eating soup from a damaged can. Black mould contaminating the can was subcultured and the fungus Penicillium crustosum was identified. This fungus usually produces a potent neurotoxin called penitrem A. The couple displayed symptoms consistent with penitrem A ingestion, all of which resolved fully. Penitrem A intoxication has been well documented in animals, but not in humans. Clinical recordsAn elderly couple was admitted to hospital after sudden onset of severe muscle tremors. The husband (aged 89) and wife (aged 84) described an uneventful morning. At about 12:00, they had shared a can of soup and toast, followed by chocolate cake, before catching a bus to the local shopping centre. They noticed the soup had a bitter taste, but dismissed the finding because it was a new brand and type to them. There had been no recent changes to their medications, and no recent exposure to garden sprays, insecticides or pesticides. Patient 1The man was first to develop symptoms. He reported feeling slightly shaky as the bus arrived at the shops at about 13:00. He had difficulty getting off the bus, his legs felt “wobbly” and he had to sit down. He developed uncontrollable shaking throughout the body, and felt sticky and sweaty. Initial assessment by ambulance officers at about 13:10 was that he had severe muscle tremors and was unable to walk, and that it was difficult to understand his speech. He had no nausea or vomiting, and his abdomen was soft. He was diaphoretic, with blood pressure 160/76 mmHg, pulse rate 80 beats/min, respiratory rate 32 breaths/min, and Glasgow Coma Score 15 out of 15. His oxygen saturation level was 85%, improving to 97% with high-flow oxygen. Subsequent assessment in hospital at 13:40 revealed that the patient’s Glasgow Coma Score had fallen to 11. Although his speech was incomprehensible, he was able to obey commands; he also displayed generalised weakness and intention tremor. He remained hypertensive and diaphoretic, but was afebrile. He later recounted (to P R L) that he had thought he was going to die. All symptoms, apart from the intention tremor, had subsided by 16:30. The patient’s medical history included chronic airway limitation, asthma, hypertension, episodic atrial fibrillation, osteoarthritis, a left total hip replacement, and an essential tremor. He had no known allergies. His medications included verapamil, digoxin, aspirin, salbutamol, tiotropium bromide, salmeterol xinafoate, quinine bisulfate prn, paracetamol and rofecoxib prn. His essential tremor remained untreated because of the contraindicated use of β-blockers in asthma. A chest x-ray was unremarkable, but electrocardiography revealed a right bundle branch block. A computed tomography brain scan showed generalised volume loss with no intracranial haemorrhage or early changes of infarction; a small low-density focus present in the right basal ganglia region was consistent with chronic lacunar infarction. The results of haematological and biochemical tests were within normal limits, except for urea (8.7 mmol/L; reference range [RR], 2.5–6.4 mmol/L), white cell count (11.2 × 109/L; RR, 4.0–11.0 × 109/L), and haemoglobin (128 g/L; RR, 130–165 g/L) (red cells were normocytic and normochromic). The patient’s blood glucose level (measured by glucometer) was 7.3 mmol/L (RR, 3.5–8.0 mmol/L). Pseudocholinesterase (13.5 U/mL; RR, 7.0–19.0 U/mL) and serum digoxin (1.5 nmol/L; RR, 1.3–2.6 nmol/L) levels were within normal limits. No urine screen for drugs was carried out. The patient was admitted for observation and investigation. The following day he was lethargic, exhausted, and displayed minimal tremor. He was eventually able to mobilise with the aid of a walking stick, as usual. Patient 2The woman had a similar presentation. She complained of feeling dizzy and shaky, but had no nausea or vomiting. Ambulance officers described her as being anxious, diaphoretic, and with uncontrollable shaking. Her blood pressure was not palpable because of severe shaking, but she was well perfused. She was tachycardic (pulse rate, 110 beats/min, taken from electrocardiographic monitoring), with a respiration rate of 20 breaths/min, temperature 36.5ºC, Glasgow Coma Score of 15, and blood glucose level (measured by glucometer) 7.0 mmol/L (RR, 3.5–8.0 mmol/L). Although she was no longer tachycardic on admission to hospital, she remained anxious and diaphoretic, with a generalised tremor that increased with stimuli (eg, being questioned). Her oxygen saturation level on room air remained above 95%. All symptoms, apart from the intention tremor, subsided by 16:30. The patient’s medical history included a left nephrectomy for calculi, right renal calculi and lithotripsy, chronic airway limitation, asthma, hypertension, and a left-eye cataract. Her medications included hydrochlorothiazide, frusemide, nitrofurantoin, aspirin, trimethoprim, salbutamol prn, beclomethasone dipropionate, quinine bisulfate prn, paracetamol prn, and Macu-Vision tablets (containing ascorbic acid, vitamin E, zinc oxide and cupric oxide). A chest x-ray and electrocardiogram were normal. A computed tomography brain scan showed no abnormality apart from a polypoid density in the inferior maxillary sinus. The results of haematological and biochemical tests were normal, except for urea (9.1 mmol/L; RR, 2.5–6.4 mmol/L) and creatinine (0.13 mmol/L; RR, 0.06–0.12 mmol/L). The level of pseudocholinesterase was within normal limits (18.7 U/mL; RR, 7.0–19.0 U/mL). A urine screen conducted for drugs of abuse (including amphetamines, methamphetamines, benzodiazepines, cocaine, opiates and cannabis) was negative. The patient was admitted for observation, and gradually improved the following day. Follow-upBoth patients were discharged 2 days after admission with a very slight residual intention tremor. When assessed by their general practitioner 2 weeks later, the man had only a mild increase in his usual essential tremor and the woman’s tremor had completely resolved. Identification of mouldThe damaged soup can was retrieved from the couple’s residence on the day of onset of their illness and sent to Food Science Australia for analysis. Examination of the can revealed a dent in the top adjacent to the ring-pull on the lid. There was black mould inside the can at the top near the damaged area, and a small amount on the underside of the lid (Box 1). The mould was subcultured onto three different media suitable for growth of common food spoilage moulds.2 The plates were incubated at 25ºC for 4 days. All plates grew a pure culture of a Penicillium species. The mould was then cultured onto identification media, incubated at 5ºC, 25ºC and 37ºC for 7 days and examined again.2 Both microscopic and colony morphology characteristics identified the mould as Penicillium crustosum. It had typical sporing structures for this species (Box 2), and its colonies on malt extract agar shed spore masses in a manner typical of the species. No mycotoxin analyses were attempted. DiscussionPenicillium crustosum is a common foodborne fungus that causes spoilage in a wide variety of foods, including meat, cereals, nuts, cheese, eggs, fruit, and processed and refrigerated foods. Almost all P. crustosum isolates produce the mycotoxin penitrem A.1-3 Its potent neurotoxic effects have been demonstrated in various laboratory animals,4,5 and naturally acquired intoxication has been reported in sheep, cattle, horses and domestic dogs.4,6-9 In animals, symptoms include ataxia, tremors and severe muscle fasciculations.4-9 Larger doses may cause seizures, massive liver necrosis and death.5 To our knowledge, there has been only one case documented in humans of a tremorgenic syndrome following ingestion of P. crustosum.10 A man who had ingested about 30 mL of beer from a can contaminated with a fungus later identified as P. crustosum developed tremorgenic syndrome. About 4 hours later, he developed headache, vomiting, diplopia, weakness and bloody diarrhoea. After 12 hours he developed a tremor. All symptoms resolved within 30 hours. In this case, the fungus isolated was found to produce the mycotoxin roquefortine, but penitrem A was not reported. The authors acknowledged that the isolate lacked a feature typical of P. crustosum. As isolates of P. crustosum almost always produce penitrem A, it is quite possible that the mould involved in this mycotoxicosis was not actually P. crustosum, but some other closely related species such as P. roqueforti.11,12 Inhalation of mouldy silage was implicated in a similar tremorgenic illness in a 16-year-old male.13 Malaise, fatigue, headache, pyrexia and vomiting occurred within hours, progressing to coarse fasciculations and tremors. Symptoms had resolved by the 7th day. A variety of fungi were isolated from the silage, including Aspergillus and Penicillium, both of which produce tremorgenic mycotoxins. Aspergillus fumigatus, which is particularly common in silage, can produce tremorgenic toxins known as fumitremorgens, but not penitrem A.14 There are strong similarities between the cases we report here and numerous documented cases of penitrem A intoxication in animals. Domestic dogs are at particular risk when they have access to household waste.6-9 P. crustosum also produces the mycotoxin roquefortine,15 whose neurotoxic effects have been implicated concurrently with those of penitrem A in some cases.7-9 However, roquefortine has been found experimentally to be far less toxic than penitrem A.15 The elderly couple experienced a comparatively rapid onset of symptoms, but had no nausea or vomiting. The differential diagnosis included a reaction [from exposure] to either a food toxin or an environmental pollutant such as a pesticide or insecticide. The canned soup was a common source of exposure, and its unusual taste further implicated the can as the toxin source. Although we did not attempt to identify the mycotoxin in the cases reported here, isolates of P. crustosum usually produce penitrem A (in one study, of 308 isolates tested, all produced penitrem A12). The highest levels of penitrem A production by P. crustosum isolates occur in liquid media,11 so the soup can in this case would have provided optimal conditions for mycotoxin synthesis. Unfortunately, none of the implicated soup remained for analysis. Most mycotoxins are heat-resistant and comparatively stable,3 so would have survived the mild cooking process. Visual impairment may have contributed to this illness occurring, in that the elderly couple were not aware that the soup can was damaged and discoloured. Experimentally, penitrem A inoculation has been found to produce a tremorgenic syndrome that leads to convulsions and death when larger doses are given.4,5 Administration of pentobarbitone has been found to be effective in controlling muscle tremors and seizures in animals.7,8 This case study highlights the need to avoid ingesting food from damaged cans. Medical and food-authority personnel should be aware of the possibility of P. crustosum ingestion and its potent neurotoxic effects. Limited reporting of this syndrome in humans suggests that it is either rare or under-reported. 1 Damaged can, showing black mould around lid 2 Sporing structures of Penicillium crustosum* * Scale bar is 10 m in length.

Peter R Lewis MB BS, DipObs, FAFPHM · Michael B Donoghue MB BS, FACEM · Lucy Cook BA(SocSc), RN · Linda V Granger BHSc, MPH · Ailsa D Hocking PhD, FAIFST, FASM

Allergic bronchopulmonary aspergillosis (ABPA) is an uncommon condition which may complicate asthma and cystic fibrosis; it is seldom considered life-threatening. We report a well 8-year-old boy with cystic fibrosis and normal lung function who progressed to respiratory failure over several days, attributable to ABPA. He recovered with non-invasive ventilation and oral corticosteroid and antifungal medications, regaining normal lung function within 2 months. To our knowledge, such an acute severe presentation of ABPA in a previously well child has not been reported before. Clinical record An 8-year-old boy with pancreatic insufficient, homozygous ΔF508 cystic fibrosis (CF) was transferred from a district hospital with a 7-day history of progressive cough, wheeze and tachypnoea, despite 4 days of broad-spectrum antibacterial therapy (intravenous flucloxacillin and cefotaxime with oral roxithromycin), frequent nebulised salbutamol, oral prednisone (2 mg/kg/day) and chest physiotherapy. There were no other systemic symptoms such as rash, myalgia, arthralgia, diarrhoea or headaches. Initial sputum cultures isolated only normal respiratory flora. The provisional diagnosis was an atypical lower respiratory tract infection, attributed to a viral infection or Mycoplasma pneumoniae. Cystic fibrosis had been diagnosed at newborn screening. His height and weight had tracked along the 10th percentile. Lung function had been normal. Previous sputum cultures had grown Staphylococcus aureus but never Pseudomonas aeruginosa or Burkholderia cepacia. He had not previously wheezed. On arrival, he was mildly dyspnoeic on supplemental mask oxygen at 6 L/minute with a blood oxygen saturation (Spo2) of 94%. He was tachypnoeic (44 breaths per minute), tachycardic (112 beats per minute), afebrile and normotensive. He had bilateral expiratory wheeze with basal crackles. Within 24 hours of transfer, our patient’s condition deteriorated, and he required more frequent nebulised salbutamol and developed signs of respiratory fatigue. At this point an arterial blood gas analysis in 12 L of mask oxygen showed: pH, 7.3; partial pressure of oxygen (Po2), 58 mmHg; partial pressure of carbon dioxide (Pco2), 62.7 mmHg; bicarbonate (Hco3) level, 30 mmol/L; and base excess, 2.7. He was transferred to the paediatric intensive care unit (PICU) for respiratory support with mask continuous positive airway pressure (CPAP). Subcutaneous emphysema developed over the chest wall and neck during the first 48 hours of his PICU admission. A full blood count showed leukocytosis (19.6 × 109/L), and his initial mycoplasma complement fixation test titre was low (< 4). The mycoplasma IgM test result was subsequently negative. Immunofluorescence and culture of nasopharyngeal secretions to isolate a viral pathogen were negative. Total serum IgE titre was 1664 IU (normal range, 0–180 IU) and the skin prick test was positive for Aspergillus fumigatus. The provisional diagnosis was changed to allergic bronchopulmonary aspergillosis (ABPA). Prednisone therapy was continued, and antifungal treatment with oral itraconazole (100 mg twice daily) was added to his therapy. His respiratory status gradually improved and he was weaned off the nasal mask CPAP after 5 days, avoiding endotracheal intubation. He had clinically apparent subcutaneous emphysema, a small pneumomediastinum, but no pneumothoraces during his PICU stay. The chest radiograph before discharge from PICU (Box 1) showed increased perihilar opacities and left lower lobe infiltrates with resolution of the pneumomediastinum and subcutaneous emphysema. His improving spirometry measurements with treatment are shown in Box 2. He was discharged on Day 13 of admission with marked improvement in symptoms and an FEV1 (forced expiratory volume in 1 second) 66% of predicted. A provisional diagnosis of ABPA was confirmed by the significantly elevated serum IgE titre, positive skinprick tests for aspergillus, positive IgG aspergillus precipitins (× 4) and clinical findings consistent with the diagnostic criteria outlined in Box 3.1-5 He received decreasing doses of oral corticosteroids over 3.5 months, as well as oral itraconazole. Within 2 months, his spirometry results had returned to normal. Predictably, he became transiently cushingoid, developed mild untreated hypertension (maximum recorded blood pressure, 116/84 mmHg), and gained 4 kg in weight, but had no glycosuria. He was weaned from corticosteroids and itraconazole, and the side effects resolved within 3 months of discontinuing corticosteroids. Ten months later, he remains well, with normal lung function. DiscussionAlllergic bronchopulmonary aspergillosis (ABPA) is an uncommon condition that can complicate asthma and cystic fibrosis (CF),6,7 and is seldom considered life-threatening.7 The rapid deterioration in the condition of our previously well patient highlights the spectrum of disease severity that can occur in ABPA, and is a reminder that not all deteriorations in respiratory function in patients with CF are attributable to Pseudomonas aeruginosa or Burkholderia cepacia.7,8 Furthermore, this patient’s prompt clinical response to systemic corticosteroids with a return to normal lung function within 2 months suggests that his prognosis will not be adversely affected.9 The presence of Aspergillus species in the sputum cultures of patients with CF has been reported in up to 57% of patients,9 yet the prevalence of ABPA is reported to be between 2% and 14%.1,6 The diagnostic criteria are listed in Box 3. ABPA is a hypersensitivity reaction to the inhalation of aspergillus spores manifesting as chronic wheeze, pulmonary infiltrates and systemic immune activation.5 This results in elevated IgE, IgG and IgA titres.9 Interestingly, although aspergillus grows in the bronchial mucus, this is not an invasive disease.3-5,9 The exact mechanism by which bronchial wall damage evolves and how this gives rise to bronchiectasis and fibrosis is poorly understood.10 Aspergillus fumigatus infection often occurs months before a clinical diagnosis of ABPA is considered. Moreover, as about 40%–50% of school-aged patients with CF have aspergillus in their sputum, comparatively few develop ABPA.3 The reasons for this are not clear, but presumably relate to genetic predisposition, host defences and environmental exposure to aspergillus. Most children with CF who develop ABPA have relatively mild symptoms, respond to treatment over weeks and can often avoid hospital admission altogether.7 Patients with ABPA complicating CF more commonly follow a course of gradually worsening lung function (because of progression of their CF related bronchiectasis) with recurring relapses of ABPA, particularly in summer and autumn, when spore levels in the environment are at their highest.9,10 Treatment of ABPA has centred on the use of systemic corticosteroids for periods of 2–6 months, reducing from doses of 1.0 mg/kg/day of prednisone.4 The adjunctive use of oral antifungals has been advocated for the treatment of ABPA complicating CF11,12 and asthma.6 The response can be dramatic, as in our patient (Box 2). Itraconazole in combination with inhaled corticosteroids was recently shown to be useful for reducing eosinophilic airway inflammation, reducing systemic immune activation and reducing severe exacerbations over a period of 16 weeks in adults with ABPA complicating asthma.13 The use of itraconazole in children is less well studied. However, a recent case series of patients aged 9 to 33 years with CF and ABPA, treated with inhaled budesonide (800–1600 μg/day) and itraconazole (400–600 mg/day), showed a high prevalence of biochemical adrenal insufficiency on adrenocorticotropin testing. This was attributed to an increased systemic budesonide concentration through a reduced or inhibited metabolism (potentially caused by itraconazole), leading to inhibited steroidogenesis.14 This reminds us to use caution when treating patients who take inhaled steroids with courses of itraconazole for exacerbations of ABPA. In conclusion, we are unable to find another case report in which a previously well child with ABPA presented with severe acute respiratory failure. This case highlights the importance of considering a diagnosis of ABPA in highly unusual presentations which may complicate cystic fibrosis. 1 Chest x-ray 3 days after admission to intensive care Shows hyperinflated lung fields, perihilar inflammatory changes, emergence of an interstitial infiltrate in the left lower lobe and a small right-sided pleural effusion. 2 Relationship between IgE levels and FEV1 (forced expiratory volume in one second) before, during and after admission Inverse relationship between IgE levels and FEV1 over time (non-linear scale), showing the drop in lung function at the peak of the disease. 3 Classic case criteria for the diagnosis of allergic bronchopulmonary aspergillosis (ABPA) in patients with cystic fibrosis1-5 Clinical deterioration (increased cough, wheezing, exercise intolerance, increased sputum, decrease in pulmonary function) Immediate cutaneous reactivity to aspergillus or presence of serum IgE from A. fumigatus Total serum IgE concentration >1000 IU/L Precipitating antibodies to A. fumigatus or serum IgG from A. fumigatus Abnormal chest x-ray (infiltrates, mucus plugging, or a change from earlier films) Adapted from the ABPA Consensus Conference of the Cystic Fibrosis Foundation4

Emma Skowronski BMedSci · Dominic A Fitzgerald PhD, FRACP

Laurelle J Burrell,* Elizabeth A Grabsch,† Alexander A Padiglione,‡ M Lindsay Grayson§ * Infectious Diseases Research Nurse, † Infection Control Scientist, § Director of Infectious Diseases, Austin Hospital, Studley Road, Heidelberg, VIC 3084; ‡ Infectious Diseases Physician, Department of Epidemiology and Preventive Medicine, Monash University (Alfred Hospital), Melbourne, VIC. Lindsay. GraysonATaustin.org.au To the Editor: Patients with end-stage renal failure are a key risk group for colonisation and infection with vancomycin-resistant enterococcus (VRE). Consequently, many renal units in Australia screen these patients regularly for VRE colonisation, to assist with infection control and treatment.1-3 Screening protocols are usually applied equally to inpatients and outpatients, even though the risk of VRE colonisation among outpatients (and therefore the cost–benefit of such screening) has not been clearly defined. To assess the prevalence of faecal VRE colonisation among haemodialysis outpatients, we conducted a cross-sectional survey of outpatients attending 12 Victorian in-centre haemodialysis units — Austin Health (four units), Southern Health (three units) and five regional haemodialysis units (Bendigo, West Gippsland, La Trobe Valley, Central Gippsland and Bairnsdale). Patients attending these units represent about a third of the state’s in-centre haemodialysis population. The study was approved by the ethics committee at each hospital, and written informed consent was obtained from all participants. All patients who attended the units between 1 October 2001 and 3 April 2002 were invited to participate. VRE faecal carriage was assessed by three rectal swabs and one faecal specimen taken on at least three separate occasions. Specimens were inoculated onto Enterococcosel agar (BBL, Sparks, USA) containing 6 μg/mL vancomycin. All cultures were processed by standard methods for VRE identification, as described previously.2,3 Of 345 available haemodialysis patients, 269 (78%) consented to participate in the study (205 [76%] metropolitan, and 64 [86%] regional; participation rate per centre, 70%–91%). The 269 patients represented approximately 30% of Victorian in-centre haemodialysis patients. Overall, 74% of participants had assessment of all three rectal swabs and a faecal specimen. VRE faecal colonisation was found in three of the 269 participants (1.1%) — two were from separate metropolitan hospitals, and one from a regional centre. All isolates were Enterococcus faecium vanB (the most common type of VRE in Australia).3 None of these three patients were known to be previously colonised. This 1.1% prevalence was substantially lower than the 3.0%–4.6% prevalence previously described in renal inpatients in Melbourne,2,3 and the 10% rate reported in the United States (where 33% of dialysis centres have one or more VRE-positive patients).1,4 Statistical comparisons of this study with our previous two Australian studies2,3 should be undertaken cautiously, as screening methods differed in specimen frequency, type and number. Bearing in mind this caveat, the rate of faecal VRE carriage was significantly lower among the haemodialysis outpatients in our current study compared with renal inpatients in a 1997 study by Grayson et al2 (3/269 v 9/194; P = 0.02 by χ2 test), but less definitely so when compared with renal inpatients in the 1998–1999 study of Padiglione et al3 (3/269 v 22/739; P = 0.09, by χ2 test). Since the outpatient study, screening surveys at our hospital have shown intermittent high rates of colonisation in renal inpatients and environmental contamination (unpublished data). Given our findings in outpatients, we believe future VRE screening protocols in Australian hospitals should focus primarily on inpatients, rather than faecally continent outpatients, who have both a low rate of colonisation and low potential risk for VRE transmission or acquisition. Good compliance with practical infection control guidelines remains important to avoid widespread dissemination of VRE in our haemodialysis centres.5

Laurelle J Burrell · Elizabeth A Grabsch · Alexander A Padiglione · M Lindsay Grayson

A program for routine health surveillance on international cruise ships visiting the Port of Sydney has been developed since 1998. Before introduction of this program, ships only reported quarantinable diseases and were not aware of the Australian requirement to report other infectious diseases. Voluntary routine reporting, developed in partnership with the cruise ship industry, provides timely information on all infectious diseases of public health interest during every cruise. During 1999–2003, the program resulted in detection of and response to 14 outbreaks of gastroenteritis or acute respiratory infection, affecting more than 1400 passengers and crew. The program has improved preventive action, and risk communication and management by cruise ship operators, and led to more timely investigation and support by public health authorities.

Mark J Ferson MD, FRACP, FAFPHM · Kelly-Anne Ressler BSc(Nutr), MPH

Craig A Aboltins,* John R Daffy,† Penny Allen‡ * Infectious Diseases Registrar, † Infectious Diseases Physician, St Vincent’s Hospital, Victoria Parade, Fitzroy, VIC 3065; ‡ Ophthalmologist, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC. craigaboltinsATnetspace.net.au To the Editor: Within the last 12 months, four injecting drug users (IDUs) who had been injecting buprenorphine presented to the Royal Victorian Eye and Ear Hospital with endogenous fungal endophthalmitis (EFE) involving Candida species. All four patients admitted that they had diverted or obtained diverted sublingual buprenorphine from the oral cavity after it was dispensed. They had dissolved the remaining drug in water and injected it intravenously. We present an illustrative case. A 28-year-old woman presented with a 4-week history of left eye pain and erythema. She had a 10-year history of intravenous drug use. Over the previous 6 months, she had been regularly injecting buprenorphine that was prescribed to a friend. The friend had been removing the partially dissolved buprenorphine from his mouth before giving it to our patient. On examination, the patient could only detect hand movement with her left eye. Fundoscopy showed vitritis with a “snow ball appearance” consistent with EFE. Treatment involved vitrectomy, intravitreal amphotericin and oral fluconazole. Candida albicans was cultured from vitreal specimens. Her visual acuity had improved to 1/60 at the time of discharge. Intravenous drug use is known to be a risk factor for EFE. Candida species are the usual causative organisms, but Aspergillus species have also been reported.1 In the 1980s, there were many reports of candida endophthalmitis in injecting drug users associated with the use of “brown” (or Iranian) heroin. The “brown” heroin required an acidic substance, often lemon juice, as a solvent. Lemon juice was shown to be the source of the candida.2 However, over the past 10 years, the heroin available in Australia has been water soluble, and sterile or tap water is usually used to dissolve the heroin before injection. None of the cases we report in this letter involved lemon juice to dissolve heroin or buprenorphine before injection. Buprenorphine has been available in Australia since 2001 for the treatment of opiate addiction. It is usually dispensed daily by pharmacies in a crushed tablet form. Pharmacists are required to watch patients place and dissolve the medication under the tongue before they leave the pharmacy. Contamination of injected buprenorphine with orally derived Candida species presents a recently recognised cause of fungal endophthalmitis in injecting drug users.3 Doctors, pharmacists and drug users need to be aware of the risk of this sight-threatening complication.

Craig A Aboltins · John R Daffy · Penny Allen

A 58-year-old man of British descent presented in 2003 with chest pain, facial flushing and elevated jugular venous pressure but no leg oedema. He had been exposed to tuberculosis in childhood, had a strongly positive tuberculin test and had been followed up in the tuberculosis surveillance program with regular chest x-rays, but had never been diagnosed with tuberculosis. Chest x-ray on presentation showed calcified plaques and masses in the pericardium and mediastinum (Box 1). Computed tomography revealed extensive calcification of the pericardium (Box 2). Coronary angiography showed 70% stenosis in the left anterior descending artery. Cardiac catheterisation showed equalisation of diastolic pressures in all four chambers, with a positive square root sign (pattern of ventricular diastolic pressure characteristic of constrictive pericarditis). Pericardiectomy with left internal mammary bypass graft to the left anterior descending artery was performed. Severe constrictive pericarditis with a thick (up to 4 mm) layer of calcium plaque was found. Two large cystic masses within a thick calcified shell were present in the posterolateral aspect of the right side of the heart and the left posterior atrioventricular groove. Both contained creamy caseous material, which was drained (Box 3). Histopathological examination was consistent with chronic calcific pericarditis with no granuloma. Microbiological examination and culture did not show any organisms. The patient was treated with a 6-month regimen for Mycobacterium tuberculosis based on his known previous exposure to tuberculosis, strongly positive tuberculin test, and the operative and pathological findings. Corticosteroid therapy, which is sometimes recommended in the treatment of tuberculosis,1,2 was not considered as the patient did not have effusive pericarditis or active tuberculosis. At 12-month follow-up, he was fully active, without angina or shortness of breath. In Australia, the annual incidence of tuberculosis is 5–6 cases per 100 000.3,4 Tuberculous pericarditis is seen in 1%–2% of all cases of pulmonary tuberculosis.5 Extensive tuberculous pericarditis is rare in Anglo–Celtic populations. 1 Chest x-ray showing calcified mass along the diaphragmatic surface of heart (A) and calcified pericardium (B). 2 Pre-operative computed tomography scan showing large calcified masses (5 cm × 4 cm) in the left posterior atrioventricular groove (A) and right atrioventricular groove posterior to the tricuspid annulus (B), with calcification throughout. 3 Intraoperative photograph showing the opened large cystic mass posterior to the right atrioventricular groove, with caseous contents (arrow).

Shiromani Goyal M Ch · Kang-Teng Lim MB BS · Cheng-Hon Yap MB BS · Elizabeth W Ryan FRACP · Morteza Mohajeri FRACS

To the Editor: The disastrous events of Boxing Day, 2004 left hundreds of thousands dead, injured or homeless across large parts of Asia. Many aid teams dispatched to affected areas are grappling with the aftermath of this catastrophe. Here, I present one of many clinical observations of what we encountered in the field. It is a clinical anecdote, but one worth sharing, as it may guide future teams in similar situations. A 62-year-old woman was admitted to hospital with a history of vague ill-health for 12 months, and a subacute illness over the 4 weeks since immersion in the tsunami, with persistant cough, dyspnoea and weakness to the point of being largely bed-bound. She was cachectic, had a fever of 37.5°C and scattered crackles in both lower lung fields. Radiology facilities were not available and she was not producing sputum. She was treated empirically with antituberculous chemotherapy, as well as broad-spectrum antibiotics in the form of amoxycillin and ciprofloxacin orally, but her condition did not improve. X-ray facilities became available soon thereafter, and a chest x-ray showed changes more in keeping with a necrotising pneumonia than tuberculosis ( [a]). Her treatment was changed to intravenous meropenem (1 g every 8 hours) and her condition was slowly improving when we left. During our 2-week posting in Banda Aceh, we saw about 6–10 patients at three hospitals presenting about a month after their immersion, with fluctuating fever; chronic, non-productive cough; and radiological evidence of bilateral, asymmetric, necrotising pneumonia with cavitation. Some patients developed empyemas and pneumothoraces ( [b]). They failed to respond to broad-spectrum antibiotics including ampicillin/gentamicin/metronidazole and ticarcillin–clavulanate/cotrimoxazole. Burkholderia pseudomallei was cultured from the pleural fluid of two of these patients, and Nocardia sp. from the sputum of another. A notable feature of these patients was their subacute presentation weeks after immersion in the tsunami, the persistence of symptoms despite other broad spectrum antibiotic therapy, and the development of radiological and clinical manifestations of necrosis with pleural involvement. Many of our patients described the wave as being “black”. In view of the immersion in muddy water in a tropical environment, B. pseudomallei is likely to have been one of the causative organisms in many of these cases. However, it has not been possible to culture B. pseudomallei from all patients, and it is likely that their infections were polymicrobial given the circumstances of their injuries. A variety of bacterial organisms, as well as fungi, have been recognised in other such situations.1-3 When we were there, Fakinah hospital provided one of the few laboratory services in Banda Aceh, and the availability of these facilities were limited as they were focused on public health surveillance. Thus, collection of specimens for culture was not routine. Furthermore, when we arrived there were no nurses, no medical records and no medication or observation charts. While the situation improved rapidly during our stay, these limitations meant that recognition of emerging clinical patterns was important. Many of the antibiotics initially used for patients with immersion injuries were ineffective in this setting, and the use of carbapenems became our first-line, or early second-line, antibiotic in post-immersion respiratory infections in Banda Aceh. Chest x-rays of patients with subacute necrotising pneumonia (a) Bilateral consolidation with scarring and early cavitation in the lower lung fields (b) Bilateral necrotising pneumonia complicated by right pneumothorax

Anthony M Allworth

The annual death toll from tuberculosis in the Indian Ocean region is 2–3 times higher than the toll from the recent tsunami A major earthquake measuring 8.9 on the Richter scale occurred off the west coast of Sumatra on 26 December 2004. 1 The quake even caused the earth to wobble in orbit. 2 The ensuing tsunami hit countries bordering the Indian Ocean. The estimated death toll exceeds 220 000. 1 The human and economic tragedy was evident to all, and national governments and international organisations have mounted an enormous relief effort. Coincidentally, seven of the tsunami-affected countries (India, Indonesia, Thailand, Bangladesh, Burma–Myanmar, Tanzania and Kenya) are among the 22 nations with the highest burdens of tuberculosis (TB). 3 Over three million new TB cases and 772 000 TB deaths occurred in these seven countries in the year 2000. 3 Similar annual statistics have been reported from these and other high-burden countries for more than 10 years. But the earth does not move! The human and economic toll is not appreciated, and an enormous global response is not mounted. The global TB situation is full of such paradoxes. It also highlights the global inequities in the distribution of healthcare services and other resources. 4 An estimated 8.3 million new TB cases and nearly 2 million TB deaths occurred worldwide in 2000. 3 Ninety-five percent of the TB cases and 98% of the deaths were in low-income countries. 4 Importantly, from Australia’s perspective, 60% of this global TB burden occurred in our neighbouring countries in South East Asia and the Western Pacific. 3 What is happening in low-income countries? In Africa, 38% of new adult TB cases in 2000 were in people who were HIV-positive. 4 HIV infection increases an individual’s susceptibility to infection and disease progression, and the increased burden of HIV-associated cases may increase TB transmission to those who are HIV-negative. HIV-related TB has swamped TB-control efforts in Africa, where case numbers increased 6.4% between 1997 and 2000. 3 Multidrug-resistant tuberculosis (MDR-TB), defined as Mycobacterium tuberculosis strains with resistance to at least isoniazid and rifampicin, is also perceived as a great threat to TB control. However, only an estimated 273 000 (3.2%) of new TB cases worldwide were multidrug resistant in 2000. 5 Mathematical modelling and other observations based on imperfect data suggest that MDR-TB strains are generally of lower reproductive fitness, and that MDR-TB will remain localised in foci such as the former Soviet Union. 5 Effective TB control in these MDR-TB-endemic foci may require additional measures, such as wider availability of drug-susceptibility testing and the use of second-line drugs under close expert supervision. 5 More mundane factors than MDR-TB are the real confounders of TB control in low-income countries. These factors include inadequate infrastructure (eg, roads, transport, electricity), weak primary healthcare systems, poor laboratory services, and insufficient engagement of private practitioners and other health providers in TB control. 6 A major impediment to TB control that must be highlighted is the lack of trained staff, particularly in HIV-endemic countries, where the epidemic has decimated the healthcare workforce. 6 What can be done in low-income countries? Effective TB control relies on halting transmission through the rapid detection and cure of infectious cases. International targets have been set to detect at least 70% of all new infectious cases and to cure at least 85% of those detected by 2005. 6 Attainment of these goals would result in a decline in TB incidence of 6%–7% per year. The World Health Organization (WHO) and the International Union Against Tuberculosis and Lung Disease have recommended and validated a policy package entitled DOTS to achieve these case detection and cure rates. The DOTS strategy contains five elements: government commitment, accurate diagnosis principally by sputum-smear microscopy, standardised short-course chemotherapy with direct observation of treatment, provision of reliable drug supplies, and systematic program monitoring. 6 Unfortunately, the WHO annual TB reports to 2003 suggest that the global targets for case detection and cure rates may not be met by 2005. Additional initiatives have been recommended, including increasing government stewardship of TB-control programs, engagement of private health practitioners in DOTS programs, and involvement of local community groups. 6 Tuberculosis and HIV-control programs in Africa and other HIV-prevalent areas must also be coordinated and integrated to achieve enhanced TB and HIV case-finding, to institute TB preventive treatment, and to establish interventions against HIV, such as antiretroviral treatment (which will also indirectly control TB). 6 High-income countries with a low incidence of TB, such as Australia, confront different challenges.7 The incidence of TB in Australia was 4.9 cases per 100 000 population in 2003, which is one of the lowest rates globally, and this incidence has remained stable since the mid-1980s.8 However, people born overseas and Indigenous Australians remain at increased risk of TB (with 9.9 and 8.5 cases per 100 000 population, respectively).8 Maintaining awareness about TB among the medical profession and governments is difficult when the overall TB incidence is so low.7 Undergraduate and postgraduate education programs must ensure that clinicians consider TB, particularly in patients from at-risk subgroups.7 Governments must continue funding specialist TB treatment services (including specially trained staff and reliable drug supplies).7 The TB services themselves must realign policies and procedures towards TB elimination, and consider innovative measures for controlling TB in the subgroups who remain at increased risk of TB.7 The National Tuberculosis Advisory Committee has addressed these issues and published a strategic plan that includes performance indicators for evaluating our national TB-control efforts.9 World TB Day on 24 March is a reminder to Australian doctors that TB is not a vanishing disease. Rather, a “tsunami of TB” occurs every year overseas. What can we do? At the clinical level, Australian doctors must “think TB” when seeing patients, particularly those from subgroups at risk of TB. Australia has laboratory and clinical expertise in TB which is being shared increasingly with our neighbouring countries. Finally, we must advocate for the Australian and other governments to provide funds for TB-control programs in our neighbouring countries, as has happened for the tsunami relief effort. Australia must do so for humanitarian reasons and for self-interest.

Ivan Bastian PhD, FRCPA