Infectious diseases

Objective: To present data on rotavirus notifications in the Northern Territory to provide knowledge about the local epidemiology of rotavirus gastroenteritis that can be used to inform the use and funding of rotavirus vaccines.Design: Retrospective analysis of data from the Northern Territory Notifiable Diseases Database.Participants and setting: Patients with cases of rotavirus infection notified to the NT Centre for Disease Control from 1 January 1995 to 31 December 2004.Main outcome measures: Patterns of rotavirus notifications over time; infection rates in Indigenous versus non-Indigenous children aged 0–5 years; age groups infected with rotavirus.Results: Numbers of rotavirus notifications over the period 1995–2004 show annual, monthly and regional variability. The rotavirus notification rate for Indigenous children aged 0–5 years was 2.75 per 100 per year, compared with 0.98 for non-Indigenous children, with a relative risk for Indigenous children of 2.17 (95% CI, 1.97–2.39) over the 10 years. Indigenous children infected with rotavirus were younger than non-Indigenous children, with median ages of 11 months and 16 months, respectively. Rotavirus gastroenteritis occurred in outbreaks, transmitted over months throughout the NT.Conclusion: Large numbers of cases of rotavirus gastroenteritis affecting Indigenous and non-Indigenous children in the NT are notified every year. The rate in Indigenous children may be decreasing relative to non-Indigenous children. An effective rotavirus vaccine could prevent significant morbidity.

Rosalie Schultz MB BS, MPH

To the Editor: Meningitis is one of the most serious infections in young children. The annual incidence of Haemophilus influenzae type b (Hib) meningitis between 1984 and 1988 was 150 per 100 000 population in Aboriginal children and 27 per 100 000 in non-Aboriginal children younger than 5 years.1 A conjugate Hib vaccination program was introduced in Western Australia in January 1993, before a nationwide program commenced in July 1993. Subsequent marked declines in incidence of Hib meningitis have been reported.2-4 However, there are no recent reports on trends in overall admissions for meningitis. The WA Data Linkage System (WADLS) encompasses statewide population-based record linkage of the statutory birth and death registers, midwives’ notification system, and hospital morbidity database,5 and is one of few such resources worldwide. As part of a larger study to determine the burden of infection in a cohort of births between 1990 and 2000 using the WADLS, we investigated hospitalisation for all-cause meningitis (International classification of diseases, 9th revision, diagnosis codes 003.21, 036.0, 047, 049.0, 054.72, 320-322) in 17 296 Aboriginal and 252 775 non-Aboriginal children younger than 2 years between 1992 and 2000. In Aboriginal infants (< 12 months), the meningitis rate fell by 41% between 1992 and 1993–1994 and by a further 54% in 1995–1996, and has remained stable since (Box). In Aboriginal children aged 12–23 months, rates declined by 44% between 1993–1994 and 1995–1996 and again by 50% in 1997–1998, and no meningitis admissions were reported in 1999–2000. In non-Aboriginal infants, meningitis rates declined by 36%, from 1.8 per 1000 child-years in 1992 to 1.2 per 1000 child-years in 1993–1994, with a further 50% decline in 1997–1998, since when rates have remained stable. Rates declined by 57% between 1992 and 1993–1994 in non-Aboriginal children aged 12–23 months, declined a further 47% in 1995–1996, and have since remained stable at about 0.2 per 1000 child-years. With the decline in meningitis admissions, the disparity between Aboriginal and non-Aboriginal children has narrowed: the relative rate (RR) of Aboriginal to non-Aboriginal meningitis admissions fell from 7.3 in 1992 to 5.0 in 1999–2000 in infants, while in children aged 12–23 months, the RR was > 7.0 in 1993–1996, fell to 3.0 in 1997–1998, and was indefinable in 1999–2000 (Box). In the absence of other relevant interventions, we attribute declines in meningitis admissions to the introduction of Hib vaccine. This is supported by other studies showing a reduction in Hib meningitis following vaccination.2-4 Retrospective data provide an opportunity to assess overall trends in admissions. Future linkages with immunisation and laboratory data will allow us to investigate pathogen-specific admissions and evaluate vaccination programs. Our findings show that substantial improvements can be achieved given government commitment to implement appropriate preventive measures. Adequate funding and continued commitment is needed to ensure these measures are accessible to all WA children. Hospital admission rate for meningitis in Aboriginal and non-Aboriginal children aged (a) < 12 months and (b) 12–23 months in Western Australia, 1992–2000 Relative rate of Aboriginal to non-Aboriginal admissions is shown at the top of each graph.

Hannah C Moore · Deborah Lehmann

BCG vaccination is no longer routinely offered to all medical students in Victoria. Practices in Australia’s 15 medical schools vary widely with respect to BCG vaccination and surveillance for tuberculosis (TB) infection during the medical course. Health care workers can be exposed to TB in Australian hospitals, but the risk is much higher if they undertake work in countries with a high prevalence of TB, such as during student electives. BCG vaccination is safe, cheap and protects 50% or more of recipients from active TB, including multidrug-resistant TB. Protection is long-lasting, requires only a single dose, and there is new evidence that BCG may prevent primary infections, not just active disease. Although BCG vaccination interferes with the interpretation of the tuberculin skin test (TST), newer tests (QuantiFERON-TB Gold, T-SPOT.TB) are unaffected by BCG vaccination. We propose a standard approach for all Australian medical students that includes screening with TST and QuantiFERON-TB Gold/T-SPOT.TB at course entry, and recommending BCG vaccination for students who test negative, provided they have not previously received BCG vaccine.

Maryza Graham MB BS · Tanya M Howley MB BS · Robert J Pierce MD, FRACP, FCCP · Paul D Johnson PhD, FRACP

A 58-year-old man presented with a 1-month history of persistent nausea, vomiting, diarrhoea and fevers. He also reported worsening shortness of breath, lower extremity swelling, and a 4.5 kg weight loss. He was febrile and hypotensive, with pedal oedema and a soft diastolic murmur over the mitral area. A white cell count and chest x-ray were normal. A transthoracic echocardiogram, performed to assess cardiac function, showed a large, highly mobile left atrial mass prolapsing into the left ventricle (Box, A [arrowed]). At urgent surgery, an 8 cm left atrial myxoma arising from the interatrial septum was resected (Box, B). Histopathological examination showed dense colonies of yeast. Histoplasma capsulatum was grown from blood cultures and cultures of the surgical specimen (Box, C). HIV testing was negative. The patient made a full recovery after completing antifungal therapy. Infected left atrial myxoma is rare. We know of only one other reported case in which Histoplasma was the infective agent.1 A: Transthoracic echocardiogram B: Surgical specimen C: Microscopic view of Histoplasma capsulatum (Gomori methenamine silver stain)

Ahmed Awab MD · Mehdi Hamadani MD · Bhanu Sud MD · Gene W Voskuhl MD

Clinical record Lesions characteristic of cutaneous anthrax A 48-year-old farmer, with a history of type 2 diabetes, hypertension and hypercholesterolaemia, presented to the local hospital with fever, malaise and inflamed lesions on his hands and arms. He reported that about 5 weeks before his presentation at hospital, he had grazed his arms while clearing the loading auger on a grain harvester on his property in south-western New South Wales. Within days of the initial injury, pimples appeared at the grazed sites and these developed into larger inflamed lesions over the following weeks. He reported that during this time he scratched one lesion and pus was released. The patient was admitted and commenced on intravenous flucloxacillin with a provisional diagnosis of cellulitis. Cutaneous anthrax was not considered as a diagnosis. Oral erythromycin was added to his treatment the following day. Swabs from the lesions were collected on the day of admission and sent to the local laboratory for routine culture. Staphylococcus aureus was isolated, as well as a Bacillus species, which was thought to be a wound contaminant. Two days after admission, a nurse at the hospital noted the appearance of the lesions and discussed the patient with infectious disease control officers in the population health unit. The nurse provided photographs, and the characteristic appearance of the lesions in a farmer from the anthrax belt raised the suspicion of cutaneous anthrax. (Figure) The centres of the lesions were depressed and some had formed black scabs. The surrounding tissue was red and oedematous with extensive swelling. These were noted as characteristic features of cutaneous anthrax eschars.1 The local laboratory then performed a gram stain of the Bacillus sp. This suggested Bacillus anthracis, and the isolate was forwarded the following day to the Institute of Clinical Pathology and Medical Research. The appearance of the lesions in a farmer from an anthrax-prone area and the Gram stain of the organism led to a provisional diagnosis of cutaneous anthrax. Antibiotic treatment was changed 2 days after admission to intravenous penicillin for 6 days. One day before discharge, the patient commenced a course of oral ciprofloxacin. The patient made a full recovery. Reference laboratory investigation Gram stain of the isolate revealed large, square-ended, gram-positive rods containing oval, central to subterminal spores that did not swell the cell. The isolate produced dull, flat, white-grey non-haemolytic colonies, 3–5 mm in diameter on horse-blood agar aerobically after 24 hours’ incubation. The colonies showed characteristic comma-shaped outgrowths along the edge and were sticky when touched with an inoculating loop. The organism was non-motile in broth medium after 4 and 24 hours’ incubation. These findings are consistent with B. anthracis. Bacterial cell wall long-chain fatty acid analysis was performed using the Microbial Identification System (MIS) (MIDI Inc., Newark, Delaware, USA). MIS identified the isolate as B. anthracis when compared with library entries on the Bioterrorism database. On cluster analysis, the isolate clustered with previous isolates of B. anthracis. The B. anthracis-specific polymerase chain reaction (PCR) assay was performed.2 Briefly, this is a PCR system that detects five target gene sequences present in the chromosome, and virulence plasmids pX01 and pX02. The chromosomal marker (Ba813) is present in all B. anthracis strains. Virulent strains of B. anthracis are encapsulated and toxigenic. Plasmids pX01 and pX02 are both required for virulence, and the absence of either results in attenuation. The PCR assay on this organism gave a positive result for all five targets Anthrax is a bacterial infection resulting from endospores of Bacillus anthracis, a gram-positive, rod-shaped bacterium, entering the body through skin abrasions or by inhalation or ingestion.1 The cutaneous form accounts for more than 90% of all human cases of anthrax worldwide.3 Anthrax is a zoonosis, and normally affects grazing animals such as sheep, cattle and goats. Animals usually become infected by ingesting anthrax spores, which remain viable in the soil for many years; the spores are resistant to desiccation and ultraviolet light.4 In New South Wales, anthrax in animals is a notifiable disease under the Stock Diseases Act 1923 administered by the NSW Department of Primary Industries (DPI). The DPI has responsibility for monitoring known anthrax properties and controlling outbreaks of animal anthrax. Most outbreaks in NSW occur in the “anthrax belt”, which runs through the middle of NSW and into northern Victoria. The area is bordered by Moree and Bourke in the north and Albury and Deniliquin in the south. About three properties per year in NSW experience an anthrax outbreak.5 Cutaneous anthrax in humans usually results from direct contact with infected animals or animal products such as wool, meat or hides, and is generally an occupational hazard. The head, forearms and hands are the most common sites of infection.4 The lesions are not usually painful, but pain may result from oedema or secondary infection. The differential diagnosis includes conditions producing papular lesions with regional lymphadenopathy. If the lesions are purulent, staphylococcal lymphadenitis is the most likely cause, although secondary staphylococcal infection may occur with cutaneous anthrax.1 Human cutaneous anthrax is rare in Australia, with the most recent cases reported in 1998 in a forklift driver in Queensland and in 1997 in a knackery worker in northern Victoria.6 The last known case in NSW occurred in 1991, in a worker who was slaughtering sheep on a property in the anthrax belt.7 Lessons from practice Human cutaneous anthrax may occur in Australia, associated with occupational exposure to infected stock or products contaminated with anthrax spores. Cutaneous anthrax eschars characteristically appear as depressed ulcers with black scabs surrounded by oedema, and are painless and not purulent. Secondary infection may produce purulent lesions and mask the clinical and laboratory diagnosis of cutaneous anthrax. Health care workers and laboratory staff in the anthrax belt should be aware of the clinical and laboratory aspects of cutaneous anthrax. The source of infection in our patient remains unclear, despite the farm being an anthrax-prone property. The farmer had not reported any recent animal anthrax on the property, although animal outbreaks had occurred in previous years. The spores might have been introduced directly from the soil at the time of the injury, or entered the wounds later following contact with soil, animals or other products contaminated with anthrax spores. Animal anthrax is more likely to occur following a climate change such as heavy rain after a prolonged drought.5,8 About a week before the farmer sustained the injury, the property, which had experienced drought for number of years, received more than 40 mm of rain. Public health action included discussion of the nature of the infection with the patient and staff of the health facility, who were reassured that cutaneous anthrax is not transmissible from person to person and that the vegetative form of the bacterium is not infectious.1 Contact was made with the regional veterinary officer of the DPI, according to arrangements that provide for the exchange of information on zoonotic diseases. Routine vaccination and surveillance of stock, as well as the rapid identification and management of animal anthrax incidents are key actions required to reduce human cutaneous anthrax. Additionally, a high level of awareness among farm workers and health care staff will support the early diagnosis and appropriate treatment of human cases. Prevention through vaccination is not possible in Australia, as a human anthrax vaccine is not registered in Australia.9 The United States Centers for Disease Control and Prevention (CDC) do not recommend prophylaxis for the prevention of cutaneous anthrax. Active surveillance is recommended where there is a continuing risk of exposure.10 Prophylaxis for inhalation anthrax exposure is recommended as a 6-week course of ciprofloxacin or doxycycline.11 Inhalation anthrax results from breathing in large numbers of anthrax spores. This concentration of spores is not usually reached in soil, and inhalation anthrax has not been described in Australia.8 The characteristic eschar lesions and the absence of fever, pain and pus, along with a history of contact with animals or animal products, should suggest anthrax.1 However, secondary infection, as occurred in our patient, can produce purulent lesions and fever and mask the initial cause of infection. Cutaneous anthrax is generally self-limiting and resolves without complications. The infection responds rapidly to antibiotic treatment, and oral penicillin is generally highly effective for cutaneous disease, rendering lesions sterile after 24 hours.1 The CDC now recommend oral ciprofloxacin or doxycycline for cutaneous anthrax. This recommendation follows the use of spores of a β-lactamase-positive anthrax strain as a bioterrorism agent.12 Spread to regional lymph nodes and septicaemia occurs in about 20% of untreated cases of cutaneous anthrax.3 Intravenous therapy with a multidrug regimen is recommended for cutaneous anthrax with systemic involvement.12 In our patient, anthrax was not initially considered as a diagnosis, which may indicate a need to raise awareness of cutaneous anthrax among health care workers in the anthrax belt. It is also important that staff working in regional pathology laboratories are aware of the tests that can be undertaken at a local level and those that need to be referred to a reference laboratory for the diagnosis of human anthrax.

Anthony Kolbe BAppSc, MPH · Marion G Yuen BAppSc · Bridget K Doyle BAppSc, DipEd

Routine infection control strategies are likely to have the most benefit There is increasing concern regarding the possibility of another influenza pandemic arising from genetic mutation or reassortment of the avian influenza strain H5N1.1-3 Governments have stockpiled billions of dollars worth of antiviral agents, even though efficacy may be limited.4 Vaccines are being developed for a disease that does not yet exist.5 Many birds have been destroyed in the hope of preventing a possible future mutation and spread of disease to humans.6 Meanwhile, since the 1918 influenza pandemic, the seasonal winter flu has killed more people than the number who died in the pandemic.7 The recent SARS epidemic was a wake-up call regarding the risk of major epidemics. While important differences exist between SARS and pandemic influenza, the experience of controlling SARS provides some lessons on how to prepare for major outbreaks. It is possible that the next global infectious disease threat will not be influenza. Improving general infection control procedures and preparedness has the potential to improve routine health care on a daily basis as well as improve our ability to manage the next pandemic (Box). The SARS epidemic was not predicted. It took time to recognise that there was an epidemic and then to identify the virus.8 Cooperation among affected countries led to a coordinated effort to improve infection control procedures and limit spread of the disease. The epidemic was controlled largely with basic epidemiological principles of outbreak management and basic infection-control strategies. Hospital infection controlInfection control in hospitals is likely to have the most benefit in controlling a pandemic. The following points need to be considered. Overcrowding: Several of the hospitals affected in the SARS outbreak were suffering from chronic overcrowding (common to all Western countries). Patients were accommodated in beds less than one metre apart and routine infection-control procedures such as hand washing and changing gowns between patients were not possible. Overcrowding in emergency departments, and hospitals generally, inevitably increases the risk of infectious disease outbreaks.9 A separation of at least one metre should be maintained between patients and staff wherever possible. Separation of patients should be routine for all patients with undifferentiated, potentially infectious, illnesses. The easiest way to enforce separation of patients and encourage hand washing and other basic infection-control behaviour is to physically separate the patients in single rooms. Hand washing: Many studies have shown that hand washing protocols are not followed. This is partly related to ward layout, but also involves training and use of innovative solutions, such as staff having small antiseptic lotion bottles around their neck. It does need concerted effort and a culture change. Masks should be used routinely when dealing with patients who have undifferentiated, potentially infectious, respiratory illnesses or any infection that can be spread by droplets or aerosolisation (eg, measles, SARS). It is unclear whether high-performance masks (eg, N95) are needed or whether fit-testing is required, but it is probably more important to wear some type of mask routinely rather than a high-performance mask intermittently. Experience suggests that known high-risk patients represent a lesser threat than an unrecognised patient presenting with what is thought to be a common condition. Both patients and staff should wear masks. Personal protective equipment should be simple, such as disposable gowns, gloves, masks and eye protection.10 Expensive and complicated equipment, if used at all, should be limited to high-risk procedures (eg, airway procedures), as it is difficult to use properly. Design flaws are present in many hospitals. Examples include turbulent ventilation across patient areas and flow of aerosolised gases between treatment areas. Negative pressure rooms are frequently in short supply, if they exist at all, and would be insufficient in a pandemic. Therefore, other strategies are needed, such as physically separating patients, using curtains as separators, and cohorting infected patients as required. The benefits of good infection control were demonstrated during the SARS epidemic, with reduced staff sickness rates and fewer common infections such as gastroenteritis.11 A recent study has shown that in-hospital infection rates with multiresistant organisms are also reduced by good basic infection control.12 Improving day-to-day infection control will also ensure staff familiarity with basic infectious disease principles and allow rapid implementation in a pandemic. It is prudent to ensure that all first-line staff are fully vaccinated for common diseases, and risk assessment should be undertaken regarding other vaccination for staff. Other lessons from SARSEpidemiological skills: Many of the hospitals and communities affected by the SARS epidemic did not have the ability to rapidly deploy skilled staff for epidemiological study of the epidemic as it unfolded. This led to delays in contact tracing and control of the outbreak. Epidemiological skills need to be readily available, either directly through the hospital, or through a regional or national facility. Agreed isolation procedures: During the SARS outbreak, there was little consensus on how to quarantine and cohort potentially affected people — both in hospitals and in the community. Planning and capability to perform these functions should be researched now. Additionally, planning for surge capacity should be part of routine health care planning.13 Coordination and oversight: A poorly integrated public health system meant policies and protocols could vary even in neighbouring communities. Governments scrambled to set up expert committees composed of individuals with varied backgrounds and no history of working together. The absence of legislation empowering governments to compel health authorities and hospitals to comply with directives led to confusion and often incomplete compliance. An agreed regional approach for an infectious disease outbreak is essential; there are many authoritative guidelines.14,15 Equally, the dangers of a profusion of lengthy guidelines must be avoided. Materials must be made available to front-line staff, and should be concise, applicable and accessible. If a major infectious disease outbreak occurs, antivirals and vaccines are unlikely to be effective initially, as it will be a new disease or mutation (whether avian flu or not). Improving routine infection control procedures within hospitals is likely to have a much greater effect on limiting a new outbreak within hospitals, as well as providing benefits on a daily basis to patients and staff. Strategies to limit an infectious disease outbreak from any likely cause Strictly follow routine precautions in hospitals: Hand washing (alcohol/non-alcohol based lotions preferable to soap and water) Wearing of masks, gowns, gloves, goggles Maintaining one metre distance between patients and staff where possible Placing patients with undifferentiated infectious disease in single rooms. Avoid overuse of complicated or expensive approaches, as they cannot be used routinely (eg, negative pressure rooms, isolation suits). Limit exposure to procedures that produce aerosolisation (eg, intubation, nebulisation). Avoid hospital overcrowding, especially in emergency departments. Have a planned approach for isolation and cohorting of large groups of potentially affected people. Develop epidemiological and disease surveillance skills. Ensure staff are up to date in regular staff vaccination schedule. Ensure health system has a sustained surge capacity.

Peter A Cameron MB BS, FACEM · Michael Schull MD, MSc, FRCPC · Matthew Cooke PhD, FCEM, FRCS(Edin)

Australia is one of the few developed countries without routine antenatal HIV screening, despite having the resources to undertake such a screening program and the availability of antiretroviral therapy. National policy recommends that only women with identified risk factors should be offered testing; however, the Royal Australian and New Zealand College of Obstetricians and Gynaecologists recommends that all pregnant women be offered HIV testing as part of their antenatal care. Knowledge of a woman's HIV status during pregnancy allows interventions to improve her health and reduce the risk of transmission of HIV to her child. A universal antenatal HIV screening program meets many of the Wilson and Jungner criteria for population-based screening programs. This should be considered in the current review of Australia's HIV testing policy.

Michelle L Giles MB BS, FRACP · Margaret E Hellard FRACP, PhD · Sharon R Lewin FRACP, PhD · Anne M Mijch MB BS, FRACP

Clinically useful CAP management guidelines are still elusive Community-acquired pneumonia (CAP) continues to generate controversy. Although CAP is common and generally mild, it can be life-threatening. For the treating clinician there are many questions. How much effort should be directed to establishing the aetiology, given that the responsible pathogen is infrequently diagnosed? Should the patient be managed in hospital or at home? Should one choose older, established antibiotics that work most of the time or broad-spectrum therapy that treats all imaginable pathogens but is probably unnecessary, has a less established safety record and is likely to contribute to increased cost of treatment and the emergence of resistance? To help clinicians with these questions, international guidelines for managing CAP have been published.1-5 However, their clinical usefulness in the Australian health care context is questionable, as they are not based on particularly robust evidence and there is marked disagreement between Europeans and North Americans on the correct approach. The North Americans recommend that extensive investigations should be avoided, many patients should be treated at home, and broad-spectrum antibiotics should be used.1-3 The British and European guidelines are less focused on treating patients at home, suggest the use of cheaper, narrow-spectrum agents, and do not recommend dual therapy to treat both “typical” (eg, pneumococcus) and “atypical” (eg, Mycoplasma, Chlamydophila or Legionella) pathogens, except in patients with more severe illness.4,5 In comparison, the Australian antibiotic guidelines6 steer a middle course, suggesting the use of the Pneumonia Severity Index (PSI)7 to guide the decision regarding the need for hospital admission but then also using the PSI as a tool to assist with empirical antibiotic selection. This latter feature is somewhat unique and is based on local (as yet, unpublished) data. Some authors have suggested that investigations for CAP aetiology are not cost-effective.8 However, these opinions are often based on studies in which sputum samples were of poor quality or were collected after antibiotics were commenced. In most cases, such investigations won’t affect choice of therapy if the doctor treats for both “typical” and “atypical” agents. However, not performing these tests will mean missing the occasional unusual cause of CAP (such as Staphylococcus aureus, Legionella, community-acquired methicillin-resistant S. aureus and gram-negative organisms such as Pseudomonas). Furthermore, for hospitalised patients, the cost of these investigations is minimal compared with the cost of inpatient stay. Neglecting these investigations could lead to inappropriate management of patients who are initially thought to have CAP but who turn out to have an illness such as urinary sepsis or endocarditis. For patients who are sufficiently ill to require admission to hospital, we recommend that at least blood cultures and sputum Gram stain and cultures be performed. Apart from clinical acumen, what other tools can be used to assess the severity of CAP in an individual patient and hence guide the decision on site of care? The two most commonly used CAP severity scoring systems are the PSI7 and CURB-65 (Confusion, elevated Urea, elevated Respiratory rate, low Blood pressure and age at least 65).9 The key purpose of the PSI is to identify CAP patients who could be safely managed at home. However, it is reasonably complex, requiring input of 20 features of patient demographics, premorbid illnesses, initial vital signs and investigation results to calculate the PSI score. In addition, the PSI gives high weighting to patient age and past history but lower weighting to potentially important clinical features such as hypoxia. Thus, young, previously well patients can be classed as having mild CAP (PSI classes I–III), despite being hypoxic and having clinically severe disease. Despite these criticisms, the PSI has been validated on over 40 000 patients and appears to be accurate for predicting 30-day mortality both in the United States and Australia.7,10 For this reason it has been recommended in the current Australian antibiotic guidelines, but its uptake by Australian doctors has been limited.11 CURB-65 has the advantage of being simpler and more focused on the severity of the episode of CAP rather than the patient’s past history. However, a disadvantage is that it appears less useful for determining who is safe to be treated at home.12,13 Neither the PSI nor CURB-65 appears particularly useful for predicting accurately whether an individual patient will require admission to an intensive care unit.14 A recent Australian study suggested a modified version of CURB-65 as being more accurate for this purpose, but this is yet to be validated.15 Given these limitations, clinicians should be mindful that features such as hypoxia, vomiting, poor social circumstances, unstable comorbid conditions and empyema often indicate the need for hospital admission regardless of the PSI or CURB-65 score. Australian recommendations for empirical therapy are much closer to those of the UK and European guidelines than the North American guidelines, promoting the use of cheaper, narrow-spectrum agents such as penicillin and doxycycline.6 It is notable that penicillin is not mentioned at all in the North American guidelines.1-3 The Australian guidelines are supported by the fact that, even in an era in which penicillin resistance appears to be increasing among some Streptococcus pneumoniae isolates, there have been no documented failures of high-dose penicillin in treating pneumococcal pneumonia or bacteraemia. In comparison, there are documented cases of treatment failure with fluoroquinolones, and the widespread use of these agents has been clearly associated with increased levels of resistance to quinolones in S. pneumoniae and other previously susceptible bacteria.16 Given the importance of these issues, a large Australian, multi-state study of CAP is currently under way, with results to be made available in the next 12 months, to better guide clinicians. In the meantime, clinicians may find our general approach to patients with CAP useful (Box). Approach to managing the patient with community-acquired pneumonia (CAP) confirmed by chest x-ray PSI = Pneumonia Severity Index. * Abnormal vital signs are respiratory rate ≥ 30 breaths/minute, heart rate ≥ 125 beats/minute, systolic blood pressure < 90 mmHg. Young patients are less likely to be tachypnoeic. † Hypoxia is defined as partial pressure of oxygen (Pao2) < 60 mmHg or oxygen saturation measured by pulse oximetry (Spo2) ≤ 90% (in patients aged ≤ 40 years, use Pao2 < 70 mmHg or Spo2 ≤ 93%). ‡ Approximate costs: sputum testing, $34; blood culture, $31; Legionella urinary antigen testing, $29.

Patrick G P Charles MB BS, FRACP · Paul D R Johnson MB BS, FRACP, PhD · M Lindsay Grayson FRACP, MD, FAFPHM

We need to know if and when this organism arrives in Australia There is world-wide concern about a new infectious diseases threat following the recent emergence, in Canada,1 the United States,2 and now Europe,3 of a highly virulent strain of Clostridium difficile (called PCR ribotype 027 in Europe and NAP1 in the US). Rates of detection of C. difficile have risen dramatically: at the Centre Hospitalier Universitaire de Sherbrooke in Quebec Province (population, 7.5 million in 2003) in Canada, the incidence among patients aged ≥ 65 years increased from 102 per 100 000 population in 1991 to 867 per 100 000 in 2003.4 C. difficile disease has been more severe, with the proportion of complicated cases in Sherbrooke increasing from 7.1% (12/169) in 1991–92 to 18.2% (71/390) in 2003,4 suggesting a more virulent strain of the organism is emerging. The Quebec Health Ministry reported a total of 7004 cases of C. difficile infection between 1 April 2003 and 31 March 2004, with 1270 deaths (a crude mortality rate of 18%).5 Loo and colleagues1 reported an attributable mortality of greater than 10% in those aged over 60 years — a remarkably high figure. C. difficile is the most commonly diagnosed cause of infectious hospital-acquired diarrhoea in developed countries. Most patients with C. difficile-associated diarrhoea have been exposed to antimicrobials that reduce “colonisation resistance” of the large intestine, allowing subsequent infection with C. difficile. Acquisition of C. difficile is facilitated by its ability to form spores that are resistant to many disinfectants, so that it remains viable in the hospital environment for long periods of time. Toxigenic isolates of C. difficile usually produce two toxins, toxin A (tcdA, an enterotoxin) and toxin B (tcdB, a cytotoxin), which are considered the major virulence factors.6 Some strains of C. difficile produce an additional toxin called binary toxin (CDT). This was first reported in 1988 but not considered important until now.1,2,7 Binary toxin producers make up the majority of the C. difficile strains isolated in the recent large outbreaks of the disease overseas.1,2 A correlation between binary toxin production and severity of diarrhoea has been demonstrated,7 and more community-acquired C. difficile-associated diarrhoea was found to be caused by binary toxin producers. To determine the effects of binary toxin alone, researchers have characterised C. difficile strains that only produce binary toxin (ie, tcdA– tcdB– CDT+ strains). Although supernatants from tcdA– tcdB– CDT+ strains of C. difficile caused fluid accumulation in a rabbit ileal loop after concentration and trypsinisation, challenge of clindamycin-treated hamsters with these strains resulted in colonisation but not diarrhoea or death, suggesting that binary toxin by itself may not cause disease.8 The significance of binary toxin clearly needs further investigation. A second important feature of this “new” organism is that it produces more toxin A and B than other strains. Production of these toxins in C. difficile is encoded by the tcdA and tcdB genes, respectively. These two genes form part of a highly stable pathogenicity locus (PaLoc), a region of the chromosome that also includes the genes tcdC, tcdR and tcdE. Toxin A variant strains fail to produce toxin A detectable by enzyme immunoassay because of a deletion in the tcdA gene. The tcdC gene is a down-regulator of toxin A and B production. The PCR ribotype 027/NAP1 strain has a deletion in the tcdC gene resulting in it no longer down-regulating, and strains produce toxin throughout the log phase of growth instead of just in the stationary phase.9 Non-toxigenic strains lack the PaLoc. The third important feature of these strains is that they are resistant to fluoroquinolone antibiotics, and excessive fluoroquinolone use appears to be a contributing factor in the recent outbreaks.10 C. difficile develops resistance to quinolones soon after exposure.11 Both the newer fluoroquinolones, such as gatifloxacin and levofloxacin, and, somewhat surprisingly, the older one, ciprofloxacin, have been implicated.10 Ciprofloxacin has always been thought of as a low-risk antimicrobial for inciting C. difficile-associated diarrhoea.12 However, once C. difficile becomes resistant to the later fluoroquinolones, it is also resistant to ciprofloxacin, and the resistance trait may become more important for initiation of disease. Another significant finding from the outbreaks reported overseas is the marked variation in C. difficile-associated diarrhoea rates among different age groups. While older people have always been at increased risk, due primarily to decreased host defences, rates in those ≥ 65 years of age have increased dramatically since 2000.13 One possible novel risk factor is exposure to gastric acid suppressants, such as histamine-2 receptor inhibitors or proton pump inhibitors. These agents have been more commonly prescribed in recent years and may be linked with the increased rates of C. difficile-associated diarrhoea in the community,14 although some case–control studies with hospital patients show no association.1,10 The importance of community onset C. difficile-associated diarrhoea was highlighted recently by a report of severe cases in previously healthy people and peripartum women.15 Is this organism in Australia yet? We do not really know because molecular typing is required to distinguish the outbreak strain from others, and this is rarely done. However, it is probably not here — there have been no reports of more severe C. difficile disease, and Australia uses less of the most incriminated fluoroquinolones than other parts of the world. A major problem is that many laboratories in Australia have moved away from culturing for C. difficile, and to save money and time are using enzyme immunoassay kits. C. difficile toxin A enzyme immunoassay kits will not detect strains that don’t produce toxin A, and toxin A + B kits will not detect binary toxin producers. This diagnostic problem is compounded by the fact that laboratories servicing general practitioners often do not examine faecal samples for C. difficile because of the continuing misconception that C. difficile-associated diarrhoea is a hospital problem only. Given the high mortality rate in recent C. difficile-associated diarrhoea cases overseas, it is important that we know if and when this organism arrives in Australia. How could this be achieved? Should C. difficile-associated diarrhoea become a notifiable disease in Australia, as happened in Canada in response to the outbreak there? This is unlikely to be particularly helpful without molecular typing to distinguish the outbreak strain. Targeted surveillance, with one or two laboratories being funded periodically to type a representative sample of isolates of C. difficile from a variety of Australian hospitals, would seem a more reasonable approach. Finally, the value of sensible policies regarding antibiotic use, and good infection control staff and procedures, cannot be over-emphasised. Antibiotic restriction can be effective in reducing C. difficile-associated diarrhoea.16 In response to the outbreak in Canada, the Quebec government recently provided CA$20 million to hospitals in the province to buy additional equipment and hire infection control staff.17 In the long term, such initiatives are likely to have an impact not only on C. difficile-associated diarrhoea but also on other infection control problem organisms, such as methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus spp.

Thomas V Riley PhD, FRCPath, FASM

To the Editor: Extended-wear silicone hydrogel contact lenses allow the convenience of 24-hour correction of refractive error and freedom from cleaning solutions and storage containers. However, they are associated with an increase in the risk of microbial keratitis when worn overnight compared with daily wear.1-5 The following cases from a single ophthalmology practice illustrate the risk to contact lens wearers when they use silicone hydrogel contact lenses overnight. A 36-year-old woman presented 11 days after sleeping with her silicone hydrogel contact lenses in overnight. She had increasing right ocular pain and photophobia over the preceding 9 days, which had not resolved with chloramphenicol drops. On examination, visual acuity was 6/18 right and 6/6 left. Corneal cultures grew Acanthamoeba, which responded to polyhexamethylene biguanide and brolene drops hourly. Her final best corrected visual acuity was 6/9 right, 5 weeks later. A 24-year-old woman presented with 2 days of left ocular pain, conjunctival injection, and epiphora following continuous silicone hydrogel contact lens use over the preceding week. On examination, visual acuity was 6/6 right and 6/18 left. A central corneal ulcer with stromal infiltrate and significant anterior chamber activity was present in her left eye (Box). Corneal cultures grew Pseudomonas aeruginosa, which responded to topical gentamicin 1% drops hourly. Her final best corrected visual acuity was 6/5 left, 3 weeks after diagnosis. An 8-year-old girl was seen 2 months after commencing continuous wear of her silicone hydrogel contact lenses for uniocular myopia. She had worn the same lenses for 4 weeks continuously when she presented with a 2-day history of right ocular irritation, photophobia, and conjunctival injection. On examination, visual acuity was 6/36 right and 6/6 left. She was commenced empirically on cephalothin 5% and gentamicin 1% drops hourly. Corneal cultures did not grow any causative organism, and her clinical condition improved significantly over the following 7 days. Her final best corrected visual acuity was 6/9 right. Although microbial keratitis may only affect a small proportion of individuals1,2,5 and our patients did not experience significant reduction in vision following treatment, microbial keratitis is potentially blinding and should not be trivialised. Silicone hydrogel contact lenses have a lower risk of associated microbial keratitis than other lens types, but they do not remove it completely. In view of this, contact lenses should not be worn overnight or for an extended period. Furthermore, a painful red eye in a contact lens wearer should be considered microbial keratitis until proven otherwise, and needs a prompt ophthalmologist referral. Microbial keratitis in a 24-year-old woman

John A Landers · John L Crompton

To the Editor: Uveitis is an intraocular inflammation which potentially leads to permanent loss of vision.1,2 Tuberculosis is considered to be an infrequent infectious cause of uveitis in the developed world. However, its recurrence as a major public health problem raises the possibility that the incidence of tuberculosis-related uveitis in the developed world may rise.3,4 Uveitis in tuberculosis is presumed to result from either direct invasion or a hypersensitivity reaction. At the ophthalmology departments of the Erasmus Medical Center and the Eye Hospital in Rotterdam, The Netherlands, all patients presenting with refractory uveitis undergo investigation for a systemic cause, including tuberculin skin testing. When ocular findings are consistent with intraocular tuberculosis, and the tuberculin skin test is positive, while no other cause of uveitis is suggested by symptoms, signs or ancillary testing, then a diagnosis of presumed intraocular tuberculosis is made. Using these criteria, eight cases of presumed intraocular tuberculosis were identified among 89 people referred with refractory uveitis between January 2002 and January 2004. Characteristics of the eight patients are shown in the Box. One patient (F) withdrew from clinical care, and another (A) later had a positive culture result for tuberculosis on lymph node biopsy. This patient had complete remission of uveitis after tuberculostatic treatment, but was excluded from this study as the aim was to assess whether antituberculosis treatment is warranted based solely on a positive tuberculin skin test. We treated the patients with a complete tuberculostatic regimen (2 months of isoniazid, rifampicin, ethambutol and pyrazinamide, followed by 4 months of isoniazid, rifampicin and ethambutol). All had been previously treated for more than 3 years with immunosuppressive drugs (mainly corticosteroids), either local or systemic, or both, without adequate response. Main outcome measures were visual acuity and degree of intraocular inflammation seen on ophthalmological examination before and on completion of antituberculosis therapy. The predominant clinical finding was blurred vision. Five patients exhibited decreased intraocular inflammation and an increase in visual acuity after antituberculosis treatment, allowing tapering of the corticosteroid treatment. One patient had no response. Improvement as part of the natural history was regarded unlikely. As our department is a tertiary referral centre for patients with uveitis, our patient population is not a representative sample of all patients with uveitis in The Netherlands. Nevertheless, our findings suggest that intraocular tuberculosis should be considered in the differential diagnois of uveitis, even in developed countries. We believe that, given our results, antituberculosis therapy is justified in patients with uveitis even when a positive tuberculin skin test is the only argument for tuberculosis as the cause of the eye disease. An additional argument for antituberculosis treatment is that many patients with uveitis refractory to immunosuppressive therapy can be adequately treated with tumour necrosis factor-α (TNF-α) blocking drugs.5 However, as severe tuberculosis infection has been described after use of these agents, antituberculosis therapy is warranted in any patient with a positive tuberculin skin test who is a candidate for TNF-α blocking therapy. Details of eight patients with presumed intraocular tuberculosis Affected eye Place of birth Visual acuity Uveitis treatment Antituberculosis treatment Patient Sex Age Uveitis Before* After* Response A M 25 Left Anterior Congo NR† NR† NR† NR† NR† B F 40 Both Posterior Cape Verde 1.8/6 (R), 1.2/6 (L) 4.8/6 (both) Local steroids HRZE, HRE Partial response, local steroids continued C F 69 Left Posterior Netherlands‡ 4.8/6 4.8/6 Local steroids HRZE, HRE Complete response, local steroids stopped D M 49 Right Posterior Surinam 0.6/6 0.8/6 Vitrectomy, local steroids HRZE, HRE No response E F 36 Both Anterior Morocco 2.4/6 (R), 3/6 (L) 4.8/6 (R), 6/6 (L) Local steroids HRZE, HRE Complete response, local steroids stopped F F 62 Both Posterior Morocco 0.6/6 (R), 0.6/6 (L) Local steroids — Lost to follow up before treatment G M 54 Right Posterior Surinam 2.4/6 5.5/6 Local and systemic steroids HRZE, HRE Partial response, systemic steroids stopped H F 19 Both Intermediate Netherlands‡ 4.3/6 (R), 1.2/6 (L) 6/6 (R), 6/6 (L) Local steroids HRZE, HRE Complete response, local steroids stopped * Before and after antituberculosis therapy. † NR = no result as patient excluded from the study. ‡ Patient C’s parents were born in The Netherlands, but Patient H’s parents were from Morocco. M = male. F = female. H = isoniazid. R = rifampicin. Z = pyrazinamide. E = ethambutol.

Paul L A van Daele · Marleen Bakker · P Martin van Hagen · G Seerp Baarsma · Robert W A M Kuijpers

To the Editor: Mycobacterium ulcerans is an environmental pathogen with a global geographic distribution and focal disease clusters. The World Health Organization considers M. ulcerans infection to be of increasing global importance, particularly in West Africa. In Australia, the clinical and pathological features were fully described in 1948, when the disease was named Bairnsdale ulcer.1 Since then, the number of cases has increased, and new focal areas continue to emerge around southern coastal Victoria.2 In Queensland, the disease is most frequently reported in the Mossman area (north of Cairns in north Queensland), where it is known as Daintree ulcer.3 However, the organism is probably more widely distributed. We describe four patients recently diagnosed with proven M. ulcerans infection in the Capricorn coast region of central Queensland (Box). The suspected epicentre of infection is around Yeppoon, approximately 1000 km south of Mossman. None of the patients had significant contact with recognised endemic areas in north Queensland or Victoria. Patient 1 had visited Townsville in July 2000, but had minimal contact with the natural environment. She undertook extensive gardening at her home in North Rockhampton, using sugar cane bagasse mulch from north Queensland. The previous occupants of her house had lived in north Queensland and left behind at her home numerous potted plants originally from that area. However, investigation of soil from potted plants, gardens and roses at the home using polymerase chain reaction (PCR) failed to detect any evidence of M. ulcerans. Patient 2 lived near a coffee plantation originally planted with seeds transported from north Queensland. Sampling of plants and soil in the area by PCR revealed no atypical mycobacteria. M. ulcerans is an environmental organism associated with bodies of water, but its specific ecological niche is unknown.4 The organism is difficult to culture from the environment but has been identified by PCR in water, biofilms, aquatic insects, snails and fish. The mode of transmission to humans remains unknown. It has shown a marked propensity for causing intense focal outbreaks in Victoria (Phillip Island and Point Lonsdale) and Queensland (Daintree region). The recognition that M. ulcerans occurs in coastal central Queensland is important, as early diagnosis of M. ulcerans infection minimises the extent of tissue debridement necessary and improves outcomes. The patients we describe had complicated disease requiring multiple debridements and, in one case, amputation. Awareness of the possibility of M. ulcerans infection is critical, as diagnosis by PCR is straightforward once the infection is considered in the differential diagnosis. In 1942, Cilento described possible M. ulcerans infections from around Rockhampton.5 Four other culture-confirmed cases were reported between 1957 and 1962 from the Glass House Mountains (Sunshine Coast)3 and Maryborough (Fraser Coast)6-8 regions in Queensland. Our four cases occurred within a small geographic area centred on Yeppoon and the suburbs of Rockhampton. If the cases previously described by Cilento were truly related to M. ulcerans, then there appears to have been a five-decade gap in identification of M. ulcerans infection in the Capricorn Coast region of central Queensland. Possible explanations for this include low organism numbers resulting in sporadic infection, focal concentrations of the organism with environmental changes, such as development, land clearing and cultivation modifying human contact, or failure to diagnose the condition. Patients who acquired the infection in central Queensland may also have been diagnosed outside the area. The increase in cases in Victoria raises the possibility of a potentially similar dramatic increase in cases in central Queensland. Consideration should be given to making M. ulcerans infection a reportable disease to enable monitoring. Four patients with Mycobacterium ulcerans infection in central Queensland Age/sex Location Presentation Site Clinical features Diagnosis Treatment 47 F North Rockhampton Sep 2000 Fifth finger (left hand) Nodule Histology, PCR Debridement, antimycobacterial antibiotics, amputation 33 F Yeppoon Jun 2003 Left knee Ulcer Histology, culture Debridement 64 M Bungundarra Aug 2004 Right elbow Ulcer Histology, PCR Multiple debridements 18 M Keppel Sands Nov 2004 Right knee Ulcer Histology, culture Multiple debridements, antimycobacterial antibiotics PCR = polymerase chain reaction. F= female. M = male.

Glenn D Francis · Michael Whitby · Marion Woods

Correction Re: “Abdominal pain and eosinophilia in suburban goat keepers”, by Anna Ralph, Matthew V N O’Sullivan, Nicholas C Sangster and John C Walker in the 1 May issue of the Journal (Med J Aust 2006; 184: 467-469). The Acknowledgements were accidentally omitted from this article, and are printed below: Further, it has been decided to add the word trichostrongylosis to the title of the electronic (eMJA) version of this article, so it becomes: “Abdominal pain and eosinophilia in suburban goat keepers — trichostrongylosis”. The html and pdf versions of this article were corrected on 14 June 2006.

Anna Ralph · Matthew V N O'Sullivan · Nicholas C Sangster · John C Walker

Objective: To determine the prevalence of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) carriage and infection among children living in an Indigenous community in Queensland.Design, setting and participants: Swabs for culture of S. aureus were collected from the nose, throat and skin wounds of primary school children.Main outcome measures: MRSA carriage, antibiotic sensitivity, genotype, and presence of the virulence factor Panton–Valentine leukocidin (PVL); and epidemiological risk factors for MRSA carriage.Results: 92 (59%) of 157 eligible children were included in the study. Twenty-seven (29%) carried S. aureus; 14 of these (15% of total) carried MRSA. MRSA was isolated from 29% of wound swabs, 8% of nose swabs, and 1% of throat swabs. Fourteen of 15 MRSA isolates were sensitive to all non-β-lactam antibiotics tested. Eight children (9%) carried CA-MRSA clonal types: six carried the Queensland clone (ST93), and two carried the South West Pacific clone (ST30). All these isolates carried the virulence factor PVL. The remaining six children carried a hospital-associated MRSA strain (ST5), negative for PVL.Conclusions: We have identified a high prevalence of CA-MRSA carriage in school children from a Queensland Indigenous community. In this setting, antibiotics with activity against CA-MRSA should be considered for empiric therapy of suspected staphylococcal infection. Larger community-based studies are needed to improve our understanding of the epidemiology of CA-MRSA, and to assist in the development of therapeutic guidelines for this important infection.

Susan Vlack FAFPHM · Leonie Cox PhD · Anton Y Peleg FRACP · Condy Canuto MAE · Christine Stewart · Alzira Conlon · Alex Stephens BSc(Hons) · Philip Giffard PhD · Flavia Huygens PhD · Adam Mollinger MB BS · Renu Vohra FRCPA · James S McCarthy FRACP

Objectives: To identify the prevalence of blood-borne viruses (BBVs) testing, counselling and vaccination services by drug and alcohol services for injecting drug users in Australia.Design, setting and participants: Cross-sectional survey of drug and alcohol agencies throughout Australia.Outcome measures: Current availability of testing, counselling and vaccination services for hepatitis B virus (HBV), hepatitis C virus (HCV) and HIV; availability of medical coverage; and barriers to greater provision of services.Results: Survey responses were provided by 222 agencies nationally (61% response rate). About three-quarters of agencies provided some access to HIV, HBV, and HCV testing and HBV vaccinations, but only a third offered these services routinely on site. HBV vaccination availability differed depending on the primary function of the agency, with drug dependence units and needle and syringe programs more likely to provide vaccination on site. The major barriers preventing agencies from providing routine on-site BBV services are lack of access to medical staff and trained personnel; the cost of providing these services; and a lack of facilities.Conclusions: The restricted provision of BBV services represents missed opportunities to reduce individual and community morbidity and to maximise the potential savings from preventable disease in relation to HBV infection. To address key barriers and patient retention issues, it is necessary to expand the role of non-medical staff, increase the use of shorter HBV vaccination schedules, and identify and maintain local clinical partnerships between public and private service providers.

Adam R Winstock MSc, MRCPsych, FAChAM · Caroline M Anderson GradDipSc(Psych), BA · Janie Sheridan PhD, MRPharmS, MPS(NZ)

A 31-year-old woman presented with a tender left axillary mass. There was no history of concurrent fevers, sweats or recent illness. She was born in Australia and had not travelled overseas recently. Examination showed a left axillary mass measuring 5 cm in diameter. There was no other lymphadenopathy, no hepatosplenomegaly, nor any breast masses. Aspiration produced 10 mL of purulent fluid. Polymorphs were seen on microscopy but no Mycobacterium spp or other organisms were grown on culture. Histological sections of an excisional biopsy showed nodules of epithelioid histiocytes and giant cells with central necrosis in fibrous stroma, consistent with necrotic granulomatous lymphadenitis (Box, A). The woman’s symptoms resolved, but the mass re-accumulated after 2 years. An autoimmune process was presumed. As the mass resolved with a trial of prednisone 25 mg daily followed by methotrexate 12.5 mg per week (as a steroid-sparing agent), no further biopsy was undertaken. After 6 months of methotrexate treatment the mass recurred. Histological sections from a repeat excisional biopsy revealed the fibrous capsule of a hydatid cyst and multiple scolices. The capsule contained a patchy mixed inflammatory infiltrate and granulomatous reaction with giant cells (Box, B). Hydatid serological testing (by indirect haemagglutination) was positive at a titre of 1 : 640. The presumed exposure was from time spent about 25 years earlier on a farm in rural New South Wales where offal was fed to working dogs. Three months after commencement of albendazole therapy, the lesion was significantly reduced in size.1 Primary axillary hydatid disease is rare, with only nine previous case reports in the literature.2,3 The causes of granulomatous lymphadenitis can be classified as infective or non-infective, and among these causes, tuberculosis is the most common aetiological agent.4 We believe this to be the first case of axillary hydatid disease presenting as necrotising granulomatous lymphadenitis. Hydatid disease should be considered in the differential diagnosis of granulomatous lymphadenitis. Histological sections of excisional biopsy of axillary mass A: First biopsy, showing a central area of necrosis (arrow) surrounded by granulomatous inflammation (haematoxylin–eosin stain, original magnification × 100). B: Second biopsy, showing the characteristic laminated membrane of a hydatid cyst with associated scolices (arrows) (haematoxylin–eosin stain, original magnification × 40).

Armand Borovik MB BS · David Massasso MB BS · Kathy Gibson BA(Hons), BM BCh, PhD

Clinical records Patient 1 A 41-year-old man presented with a 3-week history of watery diarrhoea (four to five bowel motions per day) and central abdominal pain. Two days prior, he had passed blood per rectum, for which his general practitioner had prescribed oral metronidazole without any effect. He had no nausea, vomiting, fevers or sweats. Abdominal examination was unremarkable, and he was afebrile. Blood tests showed 20% eosinophilia (1.6 × 109/L; normal range, 0–0.5 × 109/L), but were otherwise unremarkable. The result of two faecal examinations showed watery stool with occasional leukocytes, but no erythrocytes. Enzyme-linked immunosorbent assay (ELISA) for Clostridium difficile toxins A/B and immunoassay for Cryptosporidium and Giardia were negative. In accordance with local laboratory protocol, microscopy to determine faecal concentration of eggs, cysts and parasite was not performed, as there was no history of overseas travel. Colonoscopy revealed mild terminal ileitis. Biopsies of the affected area showed an eosinophilic infiltrate in the lamina propria and submucosa, but intact surface epithelium. Occasional adult worms measuring about 70 μm wide at the midbody were seen on the luminal surface (Box 1A and B), and were initially identified as Enterobius vermicularis. He was treated with two 100 mg doses of mebendazole 1 week apart. However, he re-presented 3 weeks later with no improvement in his symptoms and a persistent eosinophilia (1.4 × 109/L). On this occasion, faecal concentration was performed using formalin-ethyl acetate, and parasite eggs were detected on iodine wet mount (Box 1C). These were initially misidentified as hookworm eggs, but subsequent review confirmed that they were eggs of Trichostrongylus sp. The parasites seen on terminal ileal biopsy were also reviewed. Their morphology and dimensions (70 μm-wide body) were found to be consistent with adult Trichostrongylus.1 Further questioning revealed that the patient kept goats in a shed in his backyard in suburban Sydney. The goat manure was used as fertiliser on a nearby vegetable patch which supplied food for the household. The patient was treated with a single 13.5 mg dose of ivermectin, and his symptoms resolved. He remained symptom-free 3 months later. Patient 2 A 42-year-old vegetarian man presented with a 5-week history of severe cramping upper abdominal pain, nausea and diarrhoea. He had no fever, cough, wheeze, rash or weight loss. He had holidayed in Morocco and Spain 6 months previously. Examination showed epigastric tenderness. His blood tests showed eosinophilia of 11.0 × 109/L, peaking 11 days later at 27.7 × 109/L; his blood film was otherwise normal. There were no abnormalities on plain x-rays or computed tomography scans of the chest and abdomen. A bone marrow biopsy showed a marked eosinophilia (40%–60%), but was normocellular with a normal karyotype on cytogenetic analysis. Endoscopy showed small duodenal erosions. Biopsies of the duodenum, ileum and colon showed an inflammatory cell infiltrate, including plentiful eosinophils (Box 2). Repeated stool specimens yielded only Blastocystis hominis cysts, not considered relevant to the clinical setting. A terminal urine specimen revealed no schistosome eggs, and serological tests for Strongyloides, Fasciola and Schistosoma were negative. He was treated empirically with albendazole (400 mg orally for 3 days), with minor diminution in the frequency of abdominal cramps and diarrhoea, and later with metronidazole (400 mg orally three times daily for 1 week), without response. The patient revealed that 4 weeks before symptom onset, he had taken care of a pet goat at his house, and had used fresh goat manure as fertiliser for his lettuce and other vegetable seedlings. He ate the garden produce raw and unwashed. A sample of the goat faeces was obtained from the garden for examination (fresh samples were unavailable). Baerman isolation and iodine fixation of the goat stool showed larvae of various stages, including rhabditiform larvae (probably from soil contamination) and ensheathed larvae (presumed to have hatched from eggs which would have been present in a fresh specimen). A Trichostrongylus colubriformis larva is shown in Box 3. Since exhaustive investigation had failed to yield an alternative diagnosis, trichostrongylosis was diagnosed on the basis of this strong circumstantial evidence. The patient was subsequently treated with 15 mg of ivermectin as a single dose 24 days after his hospital admission. Within 2 days, his condition had improved dramatically, and his eosinophil count fell from 18 × 109/L to 3 × 109/L. He remained well thereafter. Trichostrongylus species are zoonotic nematode parasites, ubiquitous among herbivorous mammals worldwide. Human infection is most common in herders of sheep and goats, but may potentially be acquired from contact with faeces of other infected host animals such as cattle, camels and donkeys.2 Isolated cases or small series in humans have long been recognised in Australia: 60 cases were reported from Queensland by the Hookworm Campaign between 1923 and 1928, and more recently, five cases were detected out of 46 000 stool examinations at a Queensland laboratory between 1992 and 1995.3-7 Human prevalence data are difficult to acquire because misclassification is common, and symptoms may be mild or non-existent. Trichostrongylus eggs are most commonly mistaken for hookworm eggs, which have a similar shape, although the former are larger (73–94 × 40–53 μm), and slightly pointed at one or both ends (Box 3).2 Misidentification occurred twice in Patient 1; eggs were initially identified as those of hookworm, and adult worms seen on endoscopic biopsy as Enterobius vermicularis. Diagnostic difficulties also arise because of the long prepatent period. Even after the period of maturation from larval stage to egg-laying adults, passage of eggs may still be scanty or undetectable for some time (with reported delays of 4 months to 2 years between symptom onset and detection of eggs2,5). This probably explains the absence of detectable eggs in the stool specimens of Patient 2. When a documented travel history is not provided, stool immunoassays for Giardia and/or Cryptosporidium are now being used in many laboratories instead of the more labour-intensive traditional microscopic examination for parasites. This approach will miss a number of locally-acquired parasitic infections such as hookworm, Trichuris trichiura, Strongyloides stercoralis, Isospora belli, Fasciola hepatica and Brachylaima cribbi as well as Trichostrongylus sp. Practitioners should familiarise themselves with the methods used by their local laboratory for stool parasite examination, and request that faecal concentration and microscopy for parasites be performed, not only after travel, but also if there is a history of close contact with herbivores, or consumption of unwashed home-grown vegetables fertilised with herbivore droppings. Trichostrongylus infection can also be laboratory-acquired,3 in some cases through mouth-pipetting techniques (N C S, unpublished data). Lessons from practice Trichostrongylosis may be an under-recognised cause of eosinophilia and/or gastrointestinal symptoms in Australia. Stool microscopy for parasite eggs is the only means of diagnosing trichostrongylosis, but is no longer routinely performed by many laboratories. The eggs of Trichostrongylus sp. and hookworm are very similar and can easily be confused, even by experienced laboratory staff. People fertilising their vegetable gardens with manure from herbivores, especially goats, should be advised to thoroughly wash or cook their garden produce before consumption; efficient composting is also effective in killing larvae. The drug of choice is ivermectin, because of high rates of resistance to benzimidazoles. Adult Trichostrongylus parasites residing in the gut of an infected host produce eggs which hatch in faeces to produce larvae. Such larvae (Box 3) are difficult to distinguish from those of another parasitic genus infecting goats, Ostertagia (an organism which is non-pathogenic to humans), and may be difficult for anyone other than a trained parasitologist to distinguish from larval forms of hookworm or Strongyloides. Identification of these parasite species is usually based on features of the adult worm. The larvae pass through two free-living stages to become infective third-stage larvae. These larvae are motile and migrate to vegetation and are ingested when the vegetation is eaten. The third-stage larvae then exsheath and move to the duodenal mucosa, mature into adult worms over about 25 days, and live among the intestinal villi and mucus. Patients may be asymptomatic, with eosinophilia only noted incidentally. When symptoms are present, they are confined to the gastrointestinal tract, as there is no migratory phase. A high worm burden can lead to marked eosinophilia, desquamation of gut mucosa, and severe symptoms including epigastric pain and diarrhoea.2 The per rectum bleeding noted in Patient 1 is likely to have been a direct result of mucosal inflammation and trauma caused by adult worms attaching to intestinal epithelium. Our patients’ cases illustrate the value of a collaborative approach between medical and veterinary practitioners. Medical and veterinary parasitologists were able to facilitate diagnosis and recommend appropriate treatment (ivermectin 200 μg/kg given as a single dose), based on knowledge of resistance patterns of Trichostrongylus sp. in herbivores. Resistance to benzimidazoles is now common because of the widespread use of this anthelmintic class in grazing animals.8 The treatment failure with mebendazole in Patient 1, and initial partial response to albendazole in Patient 2, followed by complete response to ivermectin, is consistent with the efficacy of these anthelmintic agents against Trichostrongylus sp. in sheep and goat populations in Australia. Resistance to pyrantel would also be anticipated, and resistance to ivermectin is emerging.9 Human trichostrongylosis is a locally acquirable cause of eosinophilia, gastrointestinal symptoms, or both, which should be suspected and appropriately investigated in patients with a history of contact with herbivorous animals. 1 Samples from Patient 1 A: Biopsy of terminal ileum showing eosinophilic infiltrate in the lamina propria and submucosa, with a parasite on the luminal surface. B: Enlargement of parasite. C: Iodine wet mount of faecal specimen showing a Trichostrongylus egg. 2 Sample from Patient 2 Duodenal biopsy showing a profuse eosinophilic infiltrate. 3 Trichostrongylus colubriformis larva Trichostrongylus colubriformis third-stage larva obtained after culture of faeces from an artificially infected sheep.

Anna Ralph MB BS, FRACP · Matthew V N O'Sullivan MB BS, DTM · Nicholas C Sangster BSc(Vet), BVSc, PhD · John C Walker BSc, MSc, PhD

To the Editor: On 1 November 2005, the Australian states and territories introduced quadrivalent, pentavalent or hexavalent vaccines for childhood immunisations. This simplifies vaccination for young children, but may impair the ability of health services to provide primary immunisation for refugees over the age of 8 years. The Australian refugee and humanitarian program targets refugees from many countries that have poor primary health infrastructure. In the 2004–05 financial year intake, at least 75% of the 12 096 entrants under the offshore resettlement program came from countries that had immunisation coverage rates below 50% in the 1990s.1,2 Adolescents and adults from these countries generally have patchy vaccination histories and no records. According to Australian guidelines, they warrant full catch-up vaccination, often involving a primary vaccination course.3 Primary vaccination against tetanus, diphtheria and pertussis requires three doses of vaccine. The dose of diphtheria toxoid in vaccines for children or adults over 8 years of age is significantly lower than in early childhood preparations because of potential adverse effects. In 2004, the conjugated pertussis–adult diphtheria–tetanus vaccine for adolescents (Boostrix, GlaxoSmithKline) was introduced to the immunisation schedule to provide boosters against pertussis, diphtheria and tetanus. However, Boostrix has no proven efficacy for primary vaccination against pertussis and is not recommended for adolescents and adults who have no primary cover against pertussis.3,4 As monovalent pertussis vaccine is not available, refugees over the age of 8 years cannot be provided with a primary vaccination course against pertussis. Adult diphtheria–tetanus vaccination (ADT) is the most-used primary vaccine for refugees over the age of 8 years. After the introduction of Boostrix, many state and territory health departments reduced their supply of ADT to immunisation providers. Some refugee health services have attempted to meet demand for ADT by collating individual doctors’ stocks provided under the Emergency Drug (Doctors Bag) supplies section of the federally-funded Pharmaceutical Benefits Scheme, which provides for up to 15 doses of ADT per month. But this is a cumbersome and unsustainable strategy. Some jurisdictions, such as the Australian Capital Territory, supply ADT directly to refugee health service providers. All the new polyvalent childhood vaccines include inactivated polio vaccine. Unless states and territories procure monovalent polio vaccine, primary vaccination against polio for people over 8 years will remain inadequate. People from refugee backgrounds warrant the same level of protection against vaccine-preventable diseases as other Australians. The level of protection may be reduced by failure to provide suitable vaccines. We encourage state and territory health departments to stock sufficient vaccines for adult and adolescent refugees, including ADT and monovalent inactivated polio vaccine. We also recommend that the Australian Technical Advisory Group on Immunisation provide detailed advice on the needs of refugees when crafting immunisation guidelines.

Christine B Phillips MPH, MA, FRACGP · Mahomed Patel FRACCP, FFAPHM

To the Editor: Leprosy rates in Australia are low (less than one case per million population)1 and predominantly occur in Indigenous Australians and immigrants from leprosy-endemic areas.2 A 21-year-old pregnant Burundian woman had migrated to Australia in 2005 from a refugee camp in Tanzania. In the year before her arrival, she had received intermittent courses of steroids for an undefined illness characterised by fever, nightsweats and painful symmetrical peripheral polyarthritis. Three months after arriving in Australia, the patient presented to a rural hospital with a recurrence of the previous symptoms. The symptoms improved on recommencement of prednisolone treatment. The patient was transferred to the Royal North Shore Hospital, where examination revealed bilateral peripheral sensory neuropathy (confirmed by nerve conduction studies); bilateral, enlarged, tender ulnar nerves; and tender hyperpigmented 2–3 cm nodules on the upper arms, but no other skin lesions or infiltrations. Skin biopsy revealed features consistent with erythema nodosum leprosum (ENL), but no acid-fast bacilli (AFB) were detected. Slit-skin smears were also negative for AFB. Leprosy was confirmed by histopathological examination of a sural nerve biopsy, which showed AFB and granulomatous changes of leprosy. The patient commenced multidrug therapy for multibacillary leprosy, with prednisolone for ENL. Leprosy is a chronic granulomatous infection of skin and peripheral nerves with Mycobacterium leprae. Host immune responses determine the spectrum of clinical presentations. Leprosy is classified into either multibacillary disease (≥ 6 skin lesions and/or skin smears positive for AFB) or paucibacillary disease (< 6 skin lesions, with no bacilli on skin smears).3 Type 1 (reversal) reactions are delayed-type hypersensitivity reactions and manifest as neuritis and increased inflammation of pre-existing skin lesions. Type 2 reactions (ENL) are a systemic response to immune complex deposition and manifest with multiple tender nodules, fevers, neuritis, arthritis and iritis.4,5 ENL occurs exclusively in multibacillary disease in 10%–20% of patients, and negative slit-skin smears (as in our patient) are unusual. Possible explanations include undisclosed diagnosis and treatment of leprosy in Tanzania or the combination of steroid therapy and immune changes that occur during pregnancy.6 Multidrug therapy is well established and regarded as safe for pregnant women. Diagnosis of infections that are uncommon in Western countries, especially leprosy, is often delayed.7 For refugees living in remote areas, access to expertise and support may be limited. Therefore, doctors, especially those involved in refugee health, should be aware of “exotic” infections and their varied presentations. Furthermore, effective referral networks should be encouraged, as this resulted in a swift positive outcome in our case.

Sebastiaan J van Hal MB ChB · Bernard J Hudson FRACP, FRCPA

To the Editor: Australia and the other member nations of the World Health Organization’s Western Pacific Region were declared free of circulating endemic poliovirus in 2000, although the last case of endemic polio in Australia occurred in the 1970s.1 Nevertheless, the low risk of vaccine-associated paralytic poliomyelitis (VAPP) persisted through the continued use of the Sabin live attenuated oral polio vaccine (OPV) until it was replaced by the Salk inactivated polio vaccine in the National Immunisation Program from 1 November 2005.2 Despite the eradication of indigenous wild poliovirus and the removal of the risk of VAPP, Australia cannot afford to be complacent with surveillance for cases of poliomyelitis. Polio is a highly infectious disease and is quickly spread through international travel. All countries risk importation of wild poliovirus from the four remaining endemic countries (Afghanistan, India, Nigeria and Pakistan) — as occurred in Indonesia and 11 other countries during 2005.3 Until the latest outbreak, involving over 300 cases, Indonesia had not reported a single case of poliomyelitis since 1995. Genetic sequencing of the wild polioviruses from Indonesia determined that they originated in Nigeria and were related to strains isolated in Sudan, Saudi Arabia and Yemen. Australia is also at risk from imported vaccine-related strains of poliovirus, as indicated by two reports from the United States in 2005. The first was a case of imported VAPP in an unimmunised adult, who had been in close contact with an infant recently immunised with OPV, while in Costa Rica.4 The second report described isolation of OPV poliovirus type 1 with a significant number of mutations (referred to as vaccine-derived poliovirus [VDPV]) from unvaccinated members of a religious community.5 Given that OPV has not been used in the USA since 2000, the source of the virus is unknown. VDPVs have been associated with paralytic polio worldwide. It is imperative that the Australian community maintains the current high rate of polio vaccination coverage, especially for travellers, which remains the best defence against all forms of imported polio. A surveillance scheme for investigation of children with acute flaccid paralysis, the major clinical presentation of poliomyelitis, was established in Australia in 1995. It is coordinated by the National Poliovirus Reference Laboratory and the Australian Paediatric Surveillance Unit (Box). While the scheme focuses on children, specimens from patients of all ages are tested. Notification of all cases with a clinical suspicion of poliomyelitis is essential for the detection of imported polio. Surveillance for acute flaccid paralysis (AFP) within Australia Paediatricians notify cases of AFP via a monthly report card to the Australian Paediatric Surveillance Unit and submit a clinical questionnaire to the National Poliovirus Reference Laboratory (NPRL). Stool specimens from AFP cases are tested at the NPRL for isolation of poliovirus. The Australian Polio Expert Committee reviews the clinical and laboratory data to determine whether the case is compatible with poliomyelitis. The Committee reports to the Australian Government Department of Health and Ageing and the World Health Organization. Protocol for investigation of suspected polio cases Clinicians should phone the NPRL to notify the case and arrange for two stool specimens to be collected 24 hours apart (due to intermittent virus shedding) and within 14 days of onset of symptoms, for testing at the NPRL. Polio antibody testing requires acute and convalescent serum, and is only performed when there is a clinical suspicion of poliomyelitis. Contacts National Poliovirus Reference Laboratory, Victorian Infectious Diseases Reference Laboratory Phone: (03) 9342 2607; fax: (03) 9342 2665; email: polioATmh.org.au; website: http://www.vidrl.org.au/labsandunits/polio/polio_activity.htm Australian Paediatric Surveillance Unit, Children’s Hospital at Westmead Phone: (02) 9845 3005/ 9845 2200; fax: (02) 9845 3082; email: apsuATchw.edu.au; website: http://www.apsu.org.au

Bruce Thorley PhD · Kerri Anne Brussen BAppSc · Elizabeth J Elliott MD, FRACP, FRCPCH · Heath A Kelly MB BS, MPH, FAFPHM

To the Editor: Rickettsia typhi is an endemic cause of atypical pyrexial illness worldwide.1 Its non-specific presentation can lead to misdiagnoses, with overseas reports of unwarranted laparotomies in affected patients.2,3 We describe a patient with R. typhi infection presenting as cholecystitis, in whom a cholecystectomy was avoided by vigilance for R. typhi. A 51-year-old businessman presented to a general practitioner with a 5-day history of fever, sore throat, headaches and myalgia. The illness had begun a week after his return to Sydney from a business trip to major cities in Asia, his last stop being Hong Kong. Investigations revealed mild lymphopenia and thrombocytopenia, negative results on screening for malaria, and normal results on chest x-ray. A non-specific viral illness was provisionally diagnosed. A week later, the patient presented again to a GP with fever, abdominal pain, cough, dehydration and confusion. Investigations revealed lymphopenia (0.7 × 109/L; reference range [RR], 1.5–4 × 109/L], thrombocytopenia (93 × 109/L; RR, 150–400 × 109/L), and raised serum levels of bilirubin (25 μmol/L; RR, 0–17 μmol/L) and hepatic enzymes (alanine aminotransferase, 307 U/L [RR, 5–40 U/L]; alkaline phosphatase, 381 U/L [RR, 30–115 U/L]; aspartate aminotransferase, 389 U/L [RR, 5–40 U/L]; and γ-glutamyl transferase, 364 U/L [RR, < 66 U/L]. Serological tests were negative for hepatitis viruses A, B and C, and dengue and Epstein–Barr viruses. The patient was referred to an emergency department. On presentation to the hospital, the patient was febrile, with severe right upper quadrant abdominal tenderness, and a slight truncal macular rash. Abdominal computed tomography and ultrasound examination indicated cholecystitis (Box). Acute cholecystitis was diagnosed, and treatment begun with intravenous fluids, ampicillin, gentamicin and metronidazole. Following clinical improvement, the patient was discharged on Day 8 with plans for an elective cholecystectomy. In view of the atypical symptom complex, serological testing for leptospirosis, syphilis, and rickettsial, amoebic and HIV infection had been requested during his admission. Results received after discharge indicated a R. typhi antibody titre of 1:1024 (RR, < 1:128). Results of the remaining serological tests were negative. The patient was contacted, and the cholecystectomy cancelled. He has remained well. Murine typhus is a zoonosis caused by R. typhi, and is acquired from rodent flea faeces, either by bite inoculation or inhalation. Hepatobiliary involvement occurs in up to 34% of cases. Histopathology specimens show neutrophilic sinusoidal infiltrates and cloudy swelling of hepatocytes,2 but hepatocyte injury and cholestasis are transient, resolving over 1–3 weeks. Diagnosis is by serological testing: a single indirect immunofluorescent antibody (IFA) titre against R. typhi of at least 1:400; or a fourfold rise in IFA titre from the acute to the convalescent phase (2 weeks apart). The treatment of choice is doxycycline. Although the clinical course is usually benign, the mortality rate can reach 4%.1 Rickettsial diseases remain an under-reported cause of febrile illness.4 As R. typhi has now been described throughout Australasia,1,5 it is important that murine typhus is excluded in patients with atypical pyrexial illnesses and abnormal liver function results. Computed tomography and ultrasound examination in a patient with murine typhus Computed tomography on admission showed pericholecystic inflammation, suggesting acute cholecystitis, and a possible gallstone at the lower pole (arrow), which was later noted to be a fibrous septum on ultrasound examination. Ultrasound examination also showed a thickened gall bladder wall and pericholecystic fluid.

Vidyut P Suttor MB BS, BSc(Med) · Robert B Feller MB BS, PhD, FRACP

The differences between community-acquired and health care-associated MRSA explained Staphylococcus aureus is one of the most important bacterial pathogens globally. About a quarter of us carry one or other strain at any one time, and, if we develop an infection, our own colonising strain is likely to be responsible.1 All clinicians, from urban general practitioners to remote-area nurses, encounter S. aureus infections. In hospitals, S. aureus is responsible for most surgical-site infections, and their control poses a major challenge. We have no effective vaccine against S. aureus, so for 50 years we have depended on the safe and affordable β-lactam antibiotics. However, in many large Australian hospitals, patients run the risk of becoming colonised with a hospital strain of S. aureus, many of which are β-lactam resistant — “golden staph” in the vernacular.2 As β-lactam resistance is detected in the laboratory using methicillin or oxacillin, microbiologists call these strains “methicillin-resistant Staphylococcus aureus” (MRSA) (see Box 1 for acronyms). All MRSA harbour the mecA gene that encodes a modified cell wall protein to which no β-lactam antibiotic is able to bind.3 Strains of health care-associated MRSA (HA-MRSA) are usually not only resistant to β-lactam antibiotics, but also carry several other resistance genes or mutations. Typically, Australian HA-MRSA isolates are not only “methicillin-resistant” but also “multiresistant”, leaving only vancomycin and a very short list of alternatives as the last line of defence. Fortunately, when clinicians have to prescribe antibiotics for S. aureus infections, the decision has been relatively straightforward — a β-lactam such as flucloxacillin or cephalexin if the infection is community-acquired (because MRSA has been rare in the community), or vancomycin if the patient has recently been in hospital. However, in the article by Nimmo and colleagues in this edition of the Journal,4 this neat epidemiological distinction is under attack. MRSA appears to be at large in the community, and the types of infections we associate with MRSA are changing. What is going on out there? Has MRSA escaped from the hospitals? Evolution occurs far more rapidly in bacteria than in more complex organisms such as humans. Bacteria are constantly deleting and acquiring genes or mutations and trying out their new configurations in new situations. It does not particularly matter from where the genes come; any DNA will do provided it is useful. S. aureus has prospered because it is carried and spread by humans, but there is a silent competition going on between different strains of S. aureus to see which one can colonise and spread most successfully. How do we know this? Using increasingly sophisticated laboratory methods, it is possible to identify and track different strains (or clones) of S. aureus. The data reported from the Australian Group on Antimicrobial Resistance (AGAR) by Nimmo and colleagues reveal the spread in Australia of new strains of MRSA, which may actually be more virulent than HA-MRSA. These “community-acquired” MRSA (CA-MRSA) carry a distinct variant of mecA that is small enough to efficiently move between bacteria. Epidemiologically, a CA-MRSA infection is one that arises in a patient who has not had contact with the health care system (no admissions to hospital in the previous 12 months, no indwelling catheters, and not a resident of a long-term care facility). The AGAR study shows that CA-MRSA has not broken out of the hospitals, but has instead emerged independently when community strains of S. aureus have acquired mecA from other bacteria.4 And S. aureus is not just in the market for antibiotic resistance genes; any DNA that can give a competitive edge is being progressively collected and amplified. One example is the gene for Panton–Valentine leukocidin (PVL), which probably provides some selective advantage to S. aureus, but in humans contributes to necrotising pneumonia and aggressive soft tissue infection. PVL, first described in 1932,5 is now present in more than 90% of the Queensland and south-west Pacific epidemic clones of CA-MRSA reported by AGAR.4 Paradoxically, these “superbugs” are sensitive to more antibiotics than HA-MRSA. β-Lactams such as flucloxacillin and cephalexin are not active, but clindamycin and trimethoprim–sulfamethoxazole may be useful alternatives. This characteristic resistance profile has also led to yet another acronym: “NORSA”, for non-multiresistant oxacillin-resistant S. aureus.6 Confused? The picture is confusing, and it is not static. AGAR has documented the stepwise increase in the proportion of community isolates of S. aureus that are MRSA in Australia, from 4.7% in 2000 to 7.3% in 2004.4 However, these data are drawn from teaching hospitals and private pathology laboratories and do not reveal the true extent of CA-MRSA carriage in the general community. To really understand what is happening, we require a population-based study to document the prevalence and movement of these new strains in the healthy majority. Who is carrying them? Do antibiotic prescribing practices play a role? Can we “profile” the typical CA-MRSA carrier, so that we can better select which antibiotics to prescribe empirically? What if CA-MRSA gets into a hospital; will it spread and replace HA-MRSA and cause even more serious hospital-acquired infections? What will we call it then? The emergence of MRSA infections in patients without apparent risk factors poses a difficult problem for clinicians who see patients with infections likely to be caused by S. aureus, especially if the infections are severe. For patients with mild to moderate infections, obtaining appropriate cultures for susceptibility testing is important. For those with severe infections possibly caused by S. aureus, intravenous flucloxacillin remains the drug of choice, as it is more effective therapy for methicillin-susceptible S. aureus bacteraemia.7 However, if the patient is critically ill or has risk factors for CA-MRSA infection, the addition of intravenous vancomycin is warranted (see Box 2). Fifty years ago, all S. aureus strains were susceptible to penicillin, but 30 years later 80% of community strains worldwide had become penicillin-resistant, forcing us to respond with penicillinase-stable β-lactams, such as flucloxacillin and cephalexin. Nimmo and colleagues have shown that strains of CA-MRSA originally identified in Queensland, Western Australia and overseas do not respect state and national boundaries, and we are likely to see increasing rates of CA-MRSA in coming years. Some of this change results from the overuse of antibiotics, and some is the inevitable result of rapid bacterial evolution to which we will have to adapt. Meanwhile, be alert, not alarmed, but some modification of the standard approach to S. aureus infections is indicated (Box 2). 1 The ABC of MRSA MRSA = methicillin-resistant Staphylococcus aureus CA-MRSA = community-acquired MRSA HA-MRSA = health care-associated MRSA NORSA = non-multiresistant oxacillin-resistant S. aureus (also an MRSA) PVL = Panton–Valentine leukocidin, a virulence factor present in some S. aureus strains 2 Suggested interim guidelines for suspected Staphylococcus aureus infections in community patients Obtain cultures for bacterial identification and drug susceptibility testing whenever possible. Discuss with the microbiology laboratory the patterns of resistance in the local area. Incision and drainage should be considered in all cases, and may be the only treatment required. For mild infections that require antibiotics but not admission to hospital: Prescribe a β-lactam antibiotic initially (eg, flucloxacillin or cephalexin) unless allergy or documented previous CA-MRSA in the patient or the patient’s family. Review the patient. Check the culture result. If CA-MRSA is identified, follow the sensitivity pattern; clindamycin or trimethoprim–sulfamethoxazole are likely to be effective. For severe suspected community-acquired S. aureus infection: Obtain cultures, commence intravenous flucloxacillin empirically. Consider combining flucloxacillin with intravenous vancomycin if the patient is critically ill. Continue flucloxacillin and cease vancomycin if methicillin-resistant S. aureus is excluded, as flucloxacillin is more effective than vancomycin for methicillin-susceptible S. aureus infections.

Paul D R Johnson MB BS, PhD, FRACP(Infectious Diseases) · Benjamin P Howden MB BS, FRACP(Infectious Diseases), FRCPA(Microbiology) · Catherine M Bennett MAppEpid, PhD

Objective: To describe antimicrobial resistance and molecular epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) isolated in community settings in Australia.Design and setting: Survey of S. aureus isolates collected prospectively Australia-wide between July 2004 and February 2005; results were compared with those of similar surveys conducted in 2000 and 2002.Main outcome measures: Up to 100 consecutive, unique clinical isolates of S. aureus from outpatient settings were collected at each of 22 teaching hospital and five private laboratories from cities in all Australian states and territories. They were characterised by antimicrobial susceptibilities (by agar dilution methods), coagulase gene typing, pulsed-field gel electrophoresis, multilocus sequence typing, SCCmec typing and polymerase chain reaction tests for Panton–Valentine leukocidin (PVL) gene.Results: 2652 S. aureus isolates were collected, of which 395 (14.9%) were MRSA. The number of community-associated MRSA (CA-MRSA) isolates rose from 4.7% (118/2498) of S. aureus isolates in 2000 to 7.3% (194/2652) in 2004 (P = 0.001). Of the three major CA-MRSA strains, WA-1 constituted 45/257 (18%) of MRSA in 2000 and 64/395 (16%) in 2004 (P = 0.89), while the Queensland (QLD) strain increased from 13/257 (5%) to 58/395 (15%) (P = 0.0004), and the south-west Pacific (SWP) strain decreased from 33/257 (13%) to 26/395 (7%) (P = 0.01). PVL genes were detected in 90/195 (46%) of CA-MRSA strains, including 5/64 (8%) of WA-1, 56/58 (97%) of QLD, and 25/26 (96%) of SWP strains. Among health care-associated MRSA strains, all AUS-2 and AUS-3 isolates were multidrug-resistant, and UK EMRSA-15 isolates were resistant to ciprofloxacin and erythromycin (50%) or to ciprofloxacin alone (44%). Almost all (98%) of CA-MRSA strains were non-multiresistant.Conclusions: Community-onset MRSA continues to spread throughout Australia. The hypervirulence determinant PVL is often found in two of the most common CA-MRSA strains. The rapid changes in prevalence emphasise the importance of ongoing surveillance.

Graeme R Nimmo FRCPA, FASM, MPH, MSc · Geoffrey W Coombs BAppSc(Med Sc), PGDipBiomedSC · Julie C Pearson BSc(Biol) · Francis G O'Brien BAppSc, PhD · Keryn J Christiansen FRCPA · John D Turnidge FRACP, FRCPA · Iain B Gosbell MD, FRACP, FRCPA · Peter Collignon FRACP, FRCPA, FASM · Mary-Louise McLaws DPHTM, MPH, PhD

Objective: To assess obstetricians’ antenatal screening practice for blood-borne viruses (HIV, hepatitis B and C viruses [HBV and HCV]) and knowledge about management during labour and risk of transmission via breastfeeding for infected women after an educational intervention.Design: Cohort study, with surveys before and after an educational intervention.Setting and participants: Survey 1 was mailed in 2002–2003 to all 767 Fellows registered with the Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG), and Survey 2 was mailed in 2004 to the 743 of these Fellows who were still practising.Intervention: Multifaceted intervention with mail-out of survey results and a summary of recommended management, publication of two review articles in the RANZCOG journal, and an oral presentation at the RANZCOG annual scientific meeting.Main outcome measures: Self-reported frequency of antenatal screening for blood-borne viruses, change in practice based on a woman’s infection status, and advice given about risk of virus transmission via breastfeeding in Survey 2, compared with Survey 1.Results: Survey 2 (response rate, 68%) found increases from the previous survey in the proportion of respondents reporting they always offered antenatal screening for HIV, from 51% to 59%, and for HCV, from 60% to 69% (P = 0.001 for both). For women with HIV infection, the proportion of respondents always recommending elective caesarean section increased from 37% to 49% (P = 0.001) and always avoiding rupture of membranes increased from 33% to 49% (P < 0.001). The proportion who reported advising (incorrectly) that breastfeeding is associated with increased risk of transmission to the infant decreased from 34% to 25% for HBV (P = 0.01) and from 47% to 39% for HCV (P = 0.03).Conclusion: The frequency of antenatal testing for HIV and HCV is increasing in Australia. Knowledge about interventions to reduce mother-to-child transmission of HIV and knowledge of the risk of HBV and HCV transmission via breastfeeding improved after a relatively simple educational intervention.

Michelle L Giles FRACP · Suzanne M Garland FRCPA, FACSHP, MD, FRANZCOG · Sonia R Grover FRANZCOG · Sharon M Lewin FRACP, PhD · Margaret E Hellard FRACP, PhD

Staphylococcus aureus bloodstream (SAB) infections are common and serious causes of morbidity and mortality that incur considerable health care costs and are potentially preventable. It should be relatively easy for hospitals to collect data on the incidence of SAB episodes, to determine whether infections were acquired in hospital or in the community, and to establish whether they were health care associated. The proportion of SAB infections caused by methicillin-resistant S. aureus strains should be a useful indicator of the level of control of antibiotic resistance in the community and in the health care setting. Continuous monitoring of infection incidence would enable health care facilities to determine the effectiveness of interventions designed to minimise SAB infections.

Peter J Collignon FRACP, FRCPA, FASM · Irene J Wilkinson BSc(Hons), MPH, MASM · Gwendolyn L Gilbert MD, FRACP, FRCPA · M Lindsay Grayson MD, FRACP, FAFPHM · R Michael Whitby FRACP, FRCPA