Infectious diseases

To the Editor: I wish to comment on Collignon’s recent editorial on methicillin-resistant Staphylococcus aureus (MRSA).1 The crux of the piece is his argument that what we need is interventional studies, not more studies documenting the extent of environmental contamination. This echoes the sentiment held by me and other colleagues working in the areas of infectious disease, microbiology and infection control. We do need more research and we need good data to evaluate interventions. However, we need to go one step further — a step that can and should be taken now, across the country. In 2006, I was part of a small team that reviewed the infection control program of a major teaching hospital in New South Wales. It became very clear that what is needed in infection control is a change in governance. At present, there is little ownership of nosocomial infections by clinicians or hospital administrators. Infection control intervention is perceived as belonging to the infection control practitioners, and not really the business of the doctors, nurses and other health workers who are caring for the individual patient. At worst, this attitude regards the necessary barrier precautions as an annoying, meddlesome burden imposed by some external agency. Clearly, such an attitude is unlikely to result in good compliance with containment measures. Infection control units have a very important role in terms of providing advice, consultancy and monitoring. But as long as there remains a general perception that nosocomial infections are solely the province of these units, progress in control is likely to be slow. One of the recommendations of our review was to change the governance structure as it relates to nosocomial infection. Elements of this included the following: Introducing infection control into the job descriptions of senior hospital executives and heads of departments; Conducting performance appraisals of these personnel to include infection control indicators; Seeking explicit agreement from all senior medical staff regarding compliance with infection control interventions; Requiring all departments to regularly and frequently review infection control indicators; and Requiring all departments to have regular, formal education sessions in infection control for all medical and nursing staff, including junior staff. We need a change in the mindset of clinicians. They must accept responsibility for what happens to their patients, including MRSA infections. These complications are no different from any others their patients may experience during their encounter with the hospital system.

Raymond C Chan

In reply: I heartily endorse Chan’s comments. To control infections in our hospitals, we desperately need not only a change in governance, but also a change in attitude. Chief executives of all hospitals, as well as all clinicians (nurses and doctors), need to take personal responsibility for serious infections that occur frequently in our hospitals. To do so, they also need to know how often these infections occur. We need robust and transparent measures — for example, data on health care-associated Staphylococcus aureus bloodstream infections, including methicillin-resistant S. aureus (MRSA),1 and deep-seated prosthetic joint infections. In recent years, faced with rising numbers of health care-associated infections, especially MRSA infections, the United Kingdom embraced necessary changes in governance. These included the promotion and use of seven key actions,2 with active surveillance and investigation being the first on the list. One of these mandatory surveillance measures was of all bloodstream infections caused by S. aureus (including MRSA)2,3 and the investigation of all episodes caused by MRSA with a “root-cause analysis”.2,4 There are early indications that the changes have successfully reduced the number of MRSA infections: from a peak of 3955 episodes of MRSA bloodstream infection occurring between October 2003 and March 2004, the number had fallen by over 40% to 2376 episodes in the period April 2007 to September 2007.3 Prevention and control of health care-associated infections must be a core part of clinical governance and patient safety programs in all hospitals. Chief executives and all clinical directors need to be aware of the numerous factors that must be given careful attention in order to reduce health care-associated infections. More importantly, they need to ensure that all appropriate steps are taken to prevent infection. This includes basic issues such as making sure that surfaces in clinical areas are adequately cleaned5 and that hand hygiene protocols are complied with — not just some of the time, but all of the time.

Peter J Collignon

To the Editor: Parasitic infections of the respiratory tract are rare causes of haemoptysis in Western communities, and are often clinically indistinguishable from pulmonary tuberculosis.1 We report a case of a 19-year-old Burmese factory worker who presented to our outpatients department with a history of haemoptysis for 4 years. He was born in Myanmar (Burma) and lived in Malaysia for 2 years before migrating to Australia. He had no past history of significance, and denied having any contacts with tuberculosis. He was a non-smoker and was taking no regular medications. His haemoptysis started in Myanmar, but increased in frequency after he migrated to Australia. He coughed up both fresh and old blood mixed with some sputum, and complained of weight loss of 6 kg, intermittent chest pain and headaches. He had no fever, night sweats, shortness of breath, dysuria, or gastrointestinal or neurological symptoms. He appeared well, and findings of a general physical examination were unremarkable. Chest x-rays from before this presentation, which included migrant screening x-rays, were normal, but his most recent chest x-ray revealed a round lesion posteriorly. A computed tomography scan organised by the patient’s general practitioner showed an area of consolidation at the base of his left lung, not typical of tuberculosis which was the primary suspect in this case. Blood tests showed a raised white cell count of 14. 5 × 109/L (reference range [RR], 4.0–11.0 × 109/L) with a neutrophil count of 11.33 × 109/L (RR, 2.0–7.5 × 109/L) and an eosinophil count of 0.51 × 109/L (RR, 0.04–0.4 × 109/L), an erythrocyte sedimentation rate of 44 mm/h (RR, 1–10 mm/h) and C-reactive protein level of 20 mg/mL (RR, < 5 mg/mL). The result of a QuantiFERON-TB Gold test for tuberculosis was negative. Attempts to obtain sputum samples were unsuccessful, and the patient underwent a bronchoscopy that revealed white milky mucous secretions within the lower lobe of the left lung, where a bronchial lavage was performed. Microscopy of bronchial washings revealed the presence of parasitic structures consistent with Paragonimus westermani (Box 1). Therapy with praziquantel was initiated at a dose of 1200 mg orally, twice daily for 2 days. His condition improved quickly and, on review in the outpatients department 4 weeks later, he had no clinically or radiologically evident recurrence of infection. Paragonimiasis is a common endemic infection in South-East and East Asia, particularly in India, China, Japan and the Philippines. Humans acquire the infection by eating raw or undercooked crayfish and freshwater crab, in which the metacercariae encyst. Once the organisms reach the duodenum, they excyst, penetrate the gut wall, and travel through the peritoneal cavity as immature flukes. They then migrate through the diaphragm and pleural space to reach the lungs, where they form adult worms.2 Early after infection, pleuritic chest pain may develop, in some cases accompanied by a pneumothorax or pleural effusion. Later, with invasion of the lung parenchyma, low-grade fever, cough or streaky haemoptysis may develop. Once the adult worms inhabit the lungs, usually after 2 months, recurrent haemoptysis becomes the cardinal symptom.3 Pulmonary paragonimiasis is most commonly misdiagnosed as tuberculosis, owing to many similarities in the clinical pictures of the two infections (Box 2).4,5 In a patient from a known endemic area, differential diagnoses should be considered and every effort should be made to obtain sputum samples or bronchial washings to distinguish between these two conditions. Serological tests are available if sputum or washings cannot be obtained. 1 Paragonimus westermani eggs detected on microscopy of bronchial washings 2 Similarities in the clinical pictures of paragonimiasis and tuberculosis Both are endemic in the same areas Neither responds to standard antibiotics Both produce chronic symptoms Symptoms of both include: Haemoptysis Weight loss Pleural effusion Chest pain

Murad G Ibrahim · Richard Bunter · Stanley Rajasooriar · Francis Thien

Objective: To assess the efficacy of a multimodal, centrally coordinated, multisite hand hygiene culture-change program (HHCCP) for reducing rates of methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia and disease in Victorian hospitals.Design, participants and setting: A pilot HHCCP was conducted over a 24-month period (October 2004 to September 2006) in six Victorian health care institutions (4 urban, 2 rural; total beds, 2379). Subsequently, we assessed the efficacy of an identical program implemented throughout Victorian public hospitals over a 12-month period (beginning between March 2006 and July 2006).Main outcome measures: Rates of hand hygiene (HH) compliance; rates of MRSA disease (patients with bacteraemia and number of clinical isolates per 100 patient discharges [PD]).Results: Mean HH compliance improved significantly at all pilot program sites, from 21% (95% CI, 20%–22%) at baseline to 48% (95% CI, 47%–49%) at 12 months and 47% (95% CI, 46%–48%; range, 31%–75%) at 24 months. Mean baseline rates for the number of patients with MRSA bacteraemia and the number of clinical MRSA isolates were 0.05/100 PD per month (range, 0.00–0.13) and 1.39/100 PD per month (range, 0.16–2.39), respectively. These were significantly reduced after 24 months to 0.02/100 PD per month for bacteraemia (P = 0.035 for trend; 65 fewer patients with bacteraemia) and 0.73/100 PD per month for MRSA isolates (P = 0.003; 716 fewer isolates). Similar findings were noted 12 months after the statewide roll-out, with an increase in mean HH compliance (from 20% to 53%; P < 0.001) and reductions in the rates of MRSA isolates (P = 0.043) and bacteraemias (P = 0.09).Conclusions: Pilot and subsequent statewide implementation of a multimodal HHCCP was effective in significantly improving HH compliance and reducing rates of MRSA infection.

M Lindsay Grayson MD, FRACP FAFPHM · Lisa J Jarvie RN · Rhea Martin RN, MPH · Paul D R Johnson PhD, FRACP · Meryanda E Jodoin RN · Celene McMullan RN · Roger H C Gregory RN · Kaye Bellis RN · Katie Cunnington RN · Fiona L Wilson RN · Diana Quin RN, BA, MPH · Anne-Maree Kelly MB BS, FACEM

To the Editor: In Victoria from 2000 to 2006, infectious syphilis notifications (primary, secondary and early latent infections) increased about 25-fold from 0.2 cases per 100 000 population in 2000 to 4.7 cases per 100 000 population in 2006.1 The number of new diagnoses of HIV has also increased since 2004.1 After observing a few patients presenting with both syphilis and a concurrent new HIV diagnosis, we investigated the association of the two diseases using retrospective laboratory data. As the Victorian Infectious Diseases Reference Laboratory (VIDRL) incorporates the state HIV reference laboratory and also acts as the reference laboratory for syphilis serological testing, it was possible to identify the HIV status and/or time of HIV diagnosis of 85% of patients identified with infectious syphilis, based on syphilis serological findings and polymerase chain reaction testing as previously described.2 Three hundred and forty-seven male patients fulfilled the criteria for infectious syphilis in the period 1 January 2000 to 30 December 2006. This represents 68% of all patients with infectious syphilis notified to the Victorian Department of Human Services over the period. Within the group of 347 patients, there were 310 with a single episode of Treponema pallidum infection, of whom 44.5% were HIV-positive. Thirty-seven patients were reinfected with syphilis, including 21 with their first episode recorded since 2000, and 11 with a serological pattern consistent with old treated syphilis recorded before reinfection during the study period. Of the 37 patients, 33 (of whom 23 were HIV-positive) had a second recorded episode and four (of whom three were HIV-positive) had a third recorded episode within the study period. Overall, 70.3% of patients with multiple episodes of syphilis were infected with HIV. Twenty patients presented with a concurrent diagnosis of infectious syphilis and previously un-diagnosed HIV infection. The trend over time is shown in the Box. Several international studies have highlighted the disproportionate incidence of syphilis in patients infected with HIV in recent years. There is now good evidence that syphilis and HIV act synergistically with regard to both transmission and progression of both diseases.3-5 The above data clearly demonstrate the strong association between HIV infection and infectious syphilis in Victoria, and this trend continued in the first half of 2007. Given the more frequent syphilis reinfections observed in the HIV-infected group, it indicates persons with HIV form a potential reservoir for syphilis infection in this state. We would strongly recommend that any patient presenting with possible syphilis or HIV infection in Victoria or elsewhere in Australia should be tested for both diseases. Episodes of infectious syphilis in Victoria by year of infection and HIV status * Patients with evidence of prior syphilis infection at an unknown time.

David E Leslie · Nasra Higgins · Christopher K Fairley

To the Editor: A 37-year-old male Sudanese refugee presented with lethargy, nausea, abdominal discomfort and bloating. He had chronic hepatitis B and a 2-year history of hazardous levels of alcohol consumption (90 g/day). On examination, there were no features of chronic liver disease. His liver enzyme levels were elevated (alkaline phosphatase, 189 U/L [reference range (RR), 40–110 U/L], γ-glutamyltransferase, 456 U/L [RR, < 50 U/L], alanine aminotransferase, 51 U/L [RR, < 45 U/L], and aspartate aminotransferase, 53 U/L [RR, < 40 U/L]), but synthetic function was preserved and serum bilirubin level was normal. Hepatitis B virus DNA was 1.3 × 103 IU/mL, consistent with a low-level viraemia, while HBeAg and anti-HBeAb were both non-reactive. His platelet count was reduced (115 × 109/L [RR, 140–400 × 109/L]), suggesting portal hypertension. The remainder of his chronic liver disease screen was unremarkable. Endoscopy revealed four grade 1 oesophageal varices, mild portal hypertensive gastritis, and patchy erosive duodenitis. The irregular liver and periportal fibrosis seen on ultrasound (Box 1) raised the possibility of cirrhosis. Subsequently, a biopsy of the liver showed preserved liver architecture, with periportal fibrosis and active schistosomiasis (Box 2). A diagnosis of Schistosoma mansoni infection was made, based on the histological appearance of the ova. S. mansoni is the leading cause of chronic liver disease and portal hypertension in sub-Saharan Africa.1,2 Adult worms reside in mesenteric vessels, but their migrating eggs lodge in hepatic presinusoidal radicals, resulting in inflammation and granuloma formation. The inflammatory reaction eventually leads to occlusion of portal veins and secondary portal hypertension.3 Hepatocellular function usually remains normal.1 Although the “gold standard” for diagnosis of S. mansoni infection is microscopic examination of faeces, this test may be negative (as it was in this case). Serological screening is recommended, but these assays cross-react with other helminthic infections and are unable to distinguish active infections from previous exposure.1 Praziquantel should be offered to previously untreated patients with positive serology results; after a single dose, 70%–100% of patients cease to excrete eggs.1 In patients who have left S. mansoni-endemic areas, an oral dose of 60 mg/kg split in two and given several hours apart should ensure cure.1 Our patient was treated with praziquantel, with ongoing follow-up for hepatitis B and portal hypertension. In retrospect, the patient’s history and the sonographic appearances were consistent with schistosomiasis. This clinical scenario is of increasing relevance, with a growing number of people from Africa now living in Australia. 1 Liver ultrasound Ultrasound shows an irregular liver with marked periportal fibrosis. There is no intra- or extrahepatic biliary tree dilatation. The portal vein flow is antegrade. No focal hepatic lesion is seen. 2 Liver biopsy specimen Preserved round to oval parasites with ova, some with a refractile exoskeleton and small lateral spine, can be seen. The viable forms suggest active infection. The surrounding inflammation contains numerous eosinophils, with fibrous expansion of the portal tracts. The adjacent liver revealed a preserved architecture with a normal METAVIR score of A0F0 (haematoxylin–eosin stain; low-power [A] and high-power [B] magnification).

James Daveson · Graeme Macdonald

Objective: To compare infection-related mortality rates and pathogens isolated for Indigenous and non-Indigenous adult patients at Alice Springs Hospital (ASH).Design, participants and setting: Retrospective study of inhospital deaths of adults (patients aged ≥ 15 years) associated with an infection during a medical or renal admission to ASH between 1 January 2000 and 31 December 2005.Main outcome measures: Admission- and population-based infection-related mortality rates and mortality rate ratios (MRRs) for Indigenous versus non-Indigenous adults.Results: There were 513 deaths, of 351 Indigenous and 162 non-Indigenous patients. For Indigenous patients, 60% of deaths were infection-related, compared with 25% for non-Indigenous patients (P < 0.001). The admission-based infection-related MRR for Indigenous versus non-Indigenous adults was 2.2 (95% CI, 1.6–3.1) (15.3 v 6.8 deaths per 1000 admissions; P < 0.001). After adjusting for age and year of death, the population-based infection-related MRR was 11.3 (95% CI, 8.0–15.8) overall (351 v 35 deaths per 100 000 population; P < 0.001) and 31.5 (95% CI, 16.1–61.8) for patients aged < 60 years. The median age of patients who died with an infection was 49 (interquartile range [IQR], 38–67) years for Indigenous and 73 (IQR, 58–80) years for non-Indigenous patients (P < 0.001). For Indigenous patients, 56% of infection-related deaths were associated with bacterial sepsis, with half of these due to enteric organisms. Other deaths followed chronic hepatitis B infection, invasive fungal infections and complications of strongyloidiasis.Conclusion: Indigenous patients at ASH are 11 times more likely than non-Indigenous patients to die with an infectious disease. This racial disparity reflects the ongoing socioeconomic disadvantage experienced by Indigenous Australians.

Lloyd J Einsiedel PhD, FRACP · Liselle A Fernandes BMedSci(Hon) · Richard J Woodman PhD, MBiostat

Objective: To describe the influenza-related morbidity and mortality in healthy children aged under 5 years in South Australia, in order to further understand the potential role of influenza vaccination.Design and setting: We undertook a descriptive analysis of SA hospital separations data and Australian Bureau of Statistics death data for children aged under 5 years admitted to hospital for influenza. All diagnoses related to an influenza admission were examined to determine whether children were at risk of complications from influenza, according to the criteria of the National Health and Medical Research Council.Main outcome measures: Mean influenza admission rates per 100 000 population per year in children aged under 5 years between 1996 and 2006, and the proportion of children admitted to hospital who did not have a secondary diagnosis putting them at higher risk of influenza-related complications.Results: From 1996 to 2006, 649 children aged under 5 years were admitted to hospital for influenza. Mean annual admission rates per 100 000 were highest in children aged under 1 year (151.0), and decreased with age. Aboriginal and Torres Strait Islander children aged under 5 years had a mean admission rate of 161.8 per 100 000. Most children under 5 years (81%) admitted to hospital did not have an underlying illness that would put them at risk of influenza-related morbidity.Conclusion: Healthy children aged under 2 years and Aboriginal and Torres Strait Islander children under 5 years old have high rates of hospital admission, which may have implications for the target group recommendations for influenza immunisation. Currently, vaccination is recommended only for children with specified chronic diseases.

Katina D’Onise MPHTM, FRACGP · Jane C A Raupach MPH, FAFPHM, FRACGP

Objective: To examine the risk of tuberculosis (TB) in migrants a decade after their arrival in Australia.Design, setting and patients: Retrospective review of laboratory-confirmed cases of TB in migrants diagnosed between 1990 and 2004 by the state TB reference laboratory in Victoria, analysed by a multivariate model comparing migrants diagnosed 10 or more years after arrival with those diagnosed within 10 years of arrival.Main outcome measures: Time to diagnosis; characteristics of migrants diagnosed with TB, including age, sex, region of birth, site of infection, and drug resistance.Results: A third of migrants (734/1924) were diagnosed with TB 10 or more years after arrival in Australia. This group was more likely to be European-born (adjusted odds ratio [AOR], 3.4; 95% CI, 2.4–5.0) and older than 34 years (35–49 years: AOR, 3.8; 95% CI, 2.0–7.0), reflecting the longer time European migrants have been in Australia. There were two distinct European groups: European Union (EU)/Western and Central/Eastern. The Central/Eastern group were from countries with current high TB rates and, compared with the EU/Western group, were younger (mean age, 50 v 64 years) and more likely to be diagnosed within 10 years of arrival (47% v 14%; P < 0.001).Conclusion: European migrants were more likely to be diagnosed a decade or more after arrival in Australia. Once migrants from the currently high TB incidence areas of Asia and Africa have been in Australia for a similar period of time, their timing of diagnosis may resemble that for migrants from Europe. The current screening policy should be complemented with more sensitive techniques to detect latent TB.

Michelle E McPherson BSc/BA, MPH, MAppEpi · Heath Kelly MB BS, MPH, FAFPHM · Mahomed S Patel MB BCh, FRACP, FAFPHM · David Leslie MB BS, FRCPA

Streptococcus suis is known to cause sporadic infections in people who have occupational exposure to pigs and pig meat. A large outbreak occurred in China in 2005, where there was 62% mortality among those who developed toxic shock syndrome. Despite S. suis being common in pigs, this is the first published report of a human case of S. suis toxic shock syndrome in Australia. Clinical recordIn April 2007, a 41-year-old man developed sudden-onset lower abdominal pain and rigors. Fevers, headache, diarrhoea, vomiting and dizziness developed and continued throughout the day. In the evening, he presented to the emergency department of a suburban non-teaching hospital in Melbourne. He had no pre-existing illness and had worked for 5 months as a pet-food processor, handling carcasses of sheep, cattle and pigs. He had a temperature of 38.8°C and his blood pressure was 84/40 mmHg. Investigations revealed acute renal failure and slightly raised serum bilirubin levels (Box). He was presumed to have infective gastroenteritis and was given intravenous fluid replacement. Septic shock was suspected when the patient’s blood pressure failed to normalise after intravenous administration of 6 L physiological saline over 12 hours and he developed neutrophilia and disseminated intravascular coagulation (Box). The presence of multiple cuts on his hands and severe tooth decay led to suspicion of staphylococcal or streptococcal sepsis. He was given vancomycin and flucloxacillin and was transferred to the intensive care unit of a teaching hospital for inotropic support. Subsequently, culture of seven of eight blood samples taken in the first 36 hours grew α-haemolytic streptococci (on horse-blood agar). Given the patient’s poor dentition, the antibiotic therapy was changed to high-dose benzylpenicillin with gentamicin to treat possible endocarditis. API 20 Strep identification system (bioMérieux, Lyon, France) gave the profile 4641473, corresponding to Streptococcus suis II (99.9%; bioscore, 0.99). Phenotypically, the isolate was very similar to Streptococcus parasanguinis, a human viridans streptococcus that is not in the API 20 Strep database. Our isolate was confirmed as S. suis by 16S rRNA (ribosomal RNA) sequencing. A 519-base-pair fragment of the 16S rRNA gene was amplified using universal primers (unpublished sequences). The primer-binding positions corresponded to positions 21–42 and 565–583 of the Escherichia coli numbering system.1 A BLAST search on the GenBank database matched several S. suis sequences exactly (519/519 bases; 100%) and partially matched many other S. suis sequences, including type strains. The next closest match was Streptococcus bovis (≤ 94% sequence homology). On Day 7, liver function tests gave abnormal results (Box). Results of a liver ultrasound examination and a transoesophageal echocardiogram were normal. The patient received intravenous benzylpenicillin and gentamicin for 2 weeks, followed by oral amoxycillin for 1 week. The patient made a full recovery, with liver function returning to normal; he subsequently changed employment. Public health responseWe notified the Victorian Government Department of Human Services, which planned to respond if additional cases of S. suis toxic shock syndrome occurred. We also referred the case to workplace occupational health and safety investigators because of a concern that an inadequate supply of gloves and other personal protective equipment had limited their use in the workplace. A worksite visit found no evidence to substantiate these concerns. Further, there were no concerns about plant and personal hygiene, washing facilities and staff training in the most recent quarterly audit report. We are not aware of any increase in S. suis disease in the Australian pig industry around the time our patient presented. In Victoria between 2002 and 2006, most streptococcal isolates submitted to the three main veterinary laboratories were not identified to species level. Therefore, although there were at least 33 confirmed S. suis isolates from pig specimens in Victoria during this period, the true burden is unknown (Brenda McCormack, Diagnostic Laboratory Manager, Pig Health Research Unit, Victorian Government Department of Primary Industries; Mary Dep, Scientist, Atwood Veterinary Diagnostic Services; and Dr Mark Williamson, Veterinary Pathologist, Gribbles Pathology, personal communications). Around the time our patient presented, Australia’s National Animal Health Information System recorded only four cases of S. suis, in piglets in Queensland.2 DiscussionS. suis is a common pathogen in pigs, and in the developed world has been recognised as a cause of sporadic disease in humans who have occupational exposure to pigs and pig meat products.3 S. suis infection in humans recently received considerable attention following a large outbreak in China in 2005, where there were 215 cases, with 62% mortality among those who developed toxic shock syndrome.4 Sepsis originating from the skin is common in meat workers due to the frequent skin lacerations they sustain, with Streptococcus pyogenes and Staphylococcus aureus often isolated.5 Other causes of sepsis in those working with pig meat products include salmonella, campylobacter, yersinia, leptospira and brucella.6 In humans, S. suis may cause toxic shock syndrome, meningitis, arthritis, endocarditis and pneumonia.3,7 Toxic shock syndrome has a distinct presentation, as seen in our patient. The predominant features are fevers, hypotension, disseminated intravascular coagulation (often with subcutaneous haemorrhage), diarrhoea, vomiting, acute renal failure, abdominal pain and liver dysfunction.3 S. suis infection occurs after contact with infected pigs or pork via wounds or inhalation.3,7 However, symptomatic or severe infection after exposure appears to be uncommon. In Australia and other high-income countries, pigs are frequently colonised with S. suis, and the seroprevalence in pig farmers and meat workers may be as high as 21%.7,8 Measures to prevent S. suis infection in meat workers include covering skin lesions; wearing gloves; avoiding eating, drinking and smoking in work areas; and frequent hand washing.6 Measures are often less stringent in domestic slaughter of pigs, which facilitated the 2005 Chinese outbreak.4 Prohibiting domestic slaughter of pigs and assisting farmers with hygienic handling of dead or sick pigs were the major interventions used to control the Chinese outbreak.4 To our knowledge, our patient is the first human case of S. suis toxic shock syndrome in Australia. Since submission of this manuscript there have been at least three unpublished recent human cases of S. suis infection in other parts of Australia, reported in February 2008 via Ozbug, an email discussion group of the Australasian Society for Infectious Diseases. Phenotypically, S. suis resembles the viridans streptococcal species Streptococcus sanguinis, S. parasanguinis and Streptococcus gordonii, and therefore may be misidentified.9 This case demonstrates the importance of correct identification to species level, which established the occupational source of infection and prevented it being attributed to poor dental hygiene. This has implications for compensation, occupational health and safety, and public health. In conclusion, it is important to consider S. suis infection in individuals with occupational exposure to pigs, as mortality may be high without timely treatment. It is also important to inform the microbiology laboratory of exposure to pigs in cases of streptococcal sepsis and meningitis to avoid misidentification. Haematological and biochemical features of a patient with Streptococcus suis toxic shock syndrome Day after onset Reference range 0 1 7 33 Haematological analysis Haemoglobin (g/L) 124 113 115 142 130–170 White cell count (× 109/L) 4.4 24.6 21.1 10.4 4.0–11.0 Neutrophil count (× 109/L) 4.2 22.7* 13.5 5.5 2.0–8.0 Platelet count (× 109/L) 182 103 259 238 140–400 INR — 2.0 1.0 0.8–1.3 APTT (s) — 37 22 24–35 Fibrinogen (g/L) — 2.8 2.8 2.0–5.0 Biochemical analysis Sodium (mmol/L) 140 141 138 135 – 145 Potassium (mmol/L) 3.2 3.6 4.8 3.5 – 5.5 Creatinine (μmol/L) 120 120 90 50 – 110 Urea (mmol/L) 7.9 6.9 4.7 2.5 – 8.3 Albumin (g/L) 42 28 34 41 35 – 50 Alkaline phosphatase (U/L) 90 72 157 98 < 120 γ-Glutamyltransferase (U/L) — 37 113 58 < 50 Alanine aminotransferase (U/L) 17 29 86 21 < 55 Aspartate aminotransferase (U/L) — 38 59 17 < 50 Bilirubin (μmol/L) 46 38 16 15 < 19 Total protein (g/L) 63 49 65 75 60 – 82 C-reactive protein (mg/L) — 173 13 < 2 < 8 INR = international normalised ratio. APTT = activated partial thromboplastin time. * Included band forms 18.0 × 109/L. Bold indicates abnormal results.

Adrian R Tramontana MB BS · Maryza Graham MB BS · Vincent Sinickas PhD, FRACP, FRCPA · Narin Bak MPH, FRACP

To the Editor: Panton–Valentine leukocidin (PVL) is a potent necrotising toxin, which, although produced by less than 5% of all Staphylococcus aureus strains, is strongly associated with pathogenic isolates that cause recurrent furunculosis and severe necrotising pneumonia.1 The virulence of PVL-positive community-associated methicillin-resistant S. aureus (CA-MRSA) causing necrotising pneumonia was recently highlighted in the Journal.2 Conversely, PVL produced by methicillin-sensitive S. aureus (MSSA) is uncommon.1 Here, we describe a case of fulminant necrotising pneumonia caused by PVL-positive MSSA, which, to our knowledge, is the first reported case in Australia. A previously well 33-year-old man presented to the emergency department with a 48-hour history of pleuritic chest pain, fever and productive cough. On presentation, the patient was hypotensive, and in acute renal failure and hypoxemic respiratory failure (type I). Chest x-ray showed bilateral widespread air space consolidation. Despite treatment with intravenous fluid resuscitation and early broad-spectrum antibiotics (ceftriaxone, azithromycin, vancomycin and co-trimoxazole), the patient’s condition rapidly deteriorated, requiring intubation and inotropic support. Multiple blood and sputum cultures isolated MSSA. Bronchoscopy revealed widespread airway haemorrhage. A trans-oesophageal echocardiogram excluded endocarditis. Progressive leukopenia developed. Septic shock and respiratory failure worsened, despite treatment with flucloxacillin as well as maximal inotropic and ventilatory support. The patient died 72 hours after presentation from fulminant pneumonia. Polymerase chain reaction testing subsequently identified the PVL gene in the isolated MSSA. Rising rates of CA-MRSA causing recurrent furunculosis and severe necrotising pneumonia have been reported worldwide.3 Necrotising pneumonia often affects children and young adults,1 and, despite current treatments, mortality rates are over 50%.4 Our patient exhibited two major factors predictive of increased lethality: leukopenia and airway bleeding.4 PVL has been well described in CA-MRSA; it is present in at least 96% of the two predominant strains in south-east Australia.3 There is some evidence that PVL is the major pathogenic factor of CA-MRSA, although this remains controversial.5 The precise pathogenesis of PVL has not yet been discovered; however, a severe inflammatory response secondary to PVL’s cytolytic effects on polymorphonuclear leukocytes, as well as the induction of other bacterial virulence factors, are possibilities.1 Therapies directed against the PVL toxin, including antibiotics such as clindamycin that target the bacterial ribosome, or intravenous immunoglobulin, have been suggested but have little supportive data.2,3,6,7 In contrast to CA-MRSA, the PVL gene is found much less frequently in MSSA, being present in only 2% of isolates in one French study.1 Specific Australian prevalence data are lacking, but PVL-positive MSSA isolates have similar potential to cause severe invasive disease.1,6 Most cases of severe necrotising staphylococcal pneumonia and recurrent furunculosis are caused by CA-MRSA, and empirical therapy for these conditions should cover this organism. This case involving MSSA highlights the role that PVL may play in the pathogenicity of these conditions, and shows that the development of novel therapeutics directed at PVL may be of value.

Ada S-Z Cheung · Craig A Aboltins · John R Daffy · Peter A Stanley

Objective: To determine the population incidence and clinical features of Escherichia coli bacteraemia in Canberra, Australia.Design, setting and participants: Canberra (including the nearby local government areas of Queanbeyan and Yarrowlumla) has a geographically isolated population of about 366 000 people. Its six hospitals also provide tertiary medical services for the surrounding region. Confining our analysis (by residential postcodes) to Canberra residents only, we used microbiology laboratory records and population statistics to calculate the population incidence of E. coli bacteraemia from January 2000 to December 2004. Clinical data were also collected prospectively on episodes occurring within three of the hospitals.Main outcome measures: Population incidence of E. coli bacteraemia; place of acquisition of infection; focus of infection within body; recovery, new morbidity or death at 7 days.Results: During the 5-year period, 515 episodes of E. coli bacteraemia occurred in Canberra residents, an incidence of 28 per 100 000 population per year. The highest rate was in men aged ≥ 80 years (463 per 100 000). Overall, E. coli bacteraemia occurred in equal numbers in males and females, but incidence was higher in males aged < 1 year and ≥ 60 years. Most episodes occurred in people aged ≥ 60 years (316/511 [62%]) and most were community-associated (347/511 [68%]). Half the infections (257/511) had a genitourinary focus and 28% (141/511) a gastrointestinal focus. The 7-day case-fatality rate was 5%. Prostate biopsies and urinary catheters were notable preventable foci of health care-associated bacteraemia. Resistance of isolates to gentamicin (2.1%), ciprofloxacin (1.8%) and cefotaxime (0.4%) was low.Conclusions: E. coli is the most common cause of bacteraemia in Canberra, and incidence increases with age. Most cases have a community onset, but many episodes are related to health care procedures. Ongoing surveillance is important for identifying risk factors that may be modified to reduce disease.

Karina J Kennedy MB BS · Jan L Roberts RN · Peter J Collignon MB BS, FRACP, FRCPA

Three patients with Australian parasitic myositis caused by the muspiceoid nematode Haycocknema perplexum are described. Treatment with albendazole led to a slow and incomplete recovery, but treatment with steroids caused life-threatening deterioration. Clinical recordsPatient 1A 23-year-old woman presented to Cairns Base Hospital with a history of 2 years of insidiously progressive weakness, including 1 year of difficulty swallowing. She weighed 42 kg, having lost 18 kg in recent years. There had been no myalgia. The patient had grown up in Queensland and was living in Innisfail, but had travelled around Australia in the 3 previous years, visiting Western Australia, New South Wales and Victoria. Although not acutely unwell or febrile, the patient was thin, with limb weakness and proximal and distal wasting. The facial muscles were wasted and weak, but palatal and ocular movements were normal. She was unable to stand from sitting without using her arms and had bilateral foot drop, but toe extension was preserved (Box 1). Reflexes were absent at the ankles and depressed elsewhere. Sensation appeared intact. Haematological testing showed eosinophilia (1.1 × 109/L; reference range [RR], < 0.4 ×109/L), which was found to have been known since 1998. It had been assumed to be due to intestinal parasites, a common problem in North Qld, but results of subsequent serology testing for Strongyloides were negative, as were stool samples. The serum creatine kinase (CK) level was high (1370 U/L; RR, <160 U/L), and there was mild derangement of liver transaminases (alanine aminotransferase, 60 U/L; RR, < 40 U/L); aspartate aminotransferase, 52 U/L; RR, < 35 U/L). Levels of inflammatory markers were also high (erythrocyte sedimentation rate, 50 mm/h; RR 0–20 mm/h; C-reactive protein, 37 mg/L; RR, < 5 mg/L). Electromyography showed low-amplitude polyphasic potentials, consistent with myopathy, and nerve conduction studies showed a mild coexistent sensory neuropathy. A biopsy of the quadriceps showed the muscle to be pale, flaccid and atrophic. On examination of paraffin sections, the muscle appeared highly abnormal; several muscle fibres contained sarcoplasmic nematode parasites characterised by a simple cephalic end and a sharply tapered caudal end. Unlike other nematodes that cause myositis, these parasites were not encysted. There was patchy interstitial and perivascular inflammation, predominantly with lymphocytes, and numerous necrotic fibres showing florid myophagia (Box 2). The parasite stained red with Gomori’s trichrome and positive with ATPase and cytochrome oxidase. Electron microscopy showed scattered sarcoplasmic parasites. Gravid female parasites were characterised by a thin cuticle, a central triradiated oesophageal lumen, and ova (Box 3). The parasite was identified as the nematode Haycocknema perplexum.1 The patient was treated with albendazole 400 mg twice daily for 8 weeks. Percutaneous endoscopic gastrostomy provided nutritional support initially. Steroids were not used at any stage of treatment. After 2 weeks, CK had fallen to 235 U/L and C-reactive protein to 1.1 mg/L. After 2 months, the patient remained diffusely weak, with ongoing dysphagia, but was able to stand from sitting. Two months after she had completed treatment, the patient’s CK began to rise, without eosinophilia. A second biopsy, of the deltoid muscle, did not show any live parasites, but showed numerous lysosomal structures, consistent with resorption of dead parasites. Significant replacement of muscle with collagenous connective tissue was noted. Twelve months after treatment, the patient had significant ongoing muscle weakness and persistently high CK levels (about 300 U/L), but normal eosinophil counts. Patient 2A 61-year-old man was admitted to a Townsville hospital for investigation of a 3-year history of slowly progressive dysphagia and dysarthria, and 1 year of limb weakness. Concurrent medical problems included diabetes mellitus, renal impairment and biliary duct ectasia. Six months before presentation, hypercalcaemia had been noted and briefly treated with oral prednisone for presumed sarcoidosis, although serum angiotensin-converting enzyme levels were normal. The patient had grown up in Tasmania, but had moved to Mackay in North Qld more than 20 years earlier, and had not travelled outside the region since. On examination, he was unwell and cachectic, with bilateral facial and palatal weakness, diffuse limb weakness and wasting and depressed reflexes, but normal sensation. On the basis of elevated CK (1263 U/L) and inflammatory markers, high-dose oral prednisone was commenced for presumed polymyositis, pending muscle biopsy results. In retrospect, peripheral eosinophilia was known to have been present for at least 2 years. After the patient had received steroids, the eosinophil count normalised. Within days, he deteriorated, requiring admission to intensive care for ventilatory support. After the muscle biopsy results showed parasitic myositis, steroids were gradually withdrawn and albendazole was commenced. The muscle function stabilised, but a biopsy 4 weeks later showed live H. perplexum nematodes. Further biopsy after 9 weeks of treatment showed no live nematodes. The intensive care stay was complicated by dependence on ventilation, sepsis, pneumonia, renal and hepatic failure and encephalopathy. Seven months later he was discharged to a regional hospital for convalescence but died from complications of sepsis and renal failure. Patient 3A 61-year-old man from Mackay, Qld, was admitted to Townsville Hospital with a 2-year history of hand cramping, progressive diffuse weakness eventually causing difficulty climbing stairs, and 1 year of dysphagia. He had lived in North Qld all his life, and had never travelled to Victoria or Tasmania. He had never consumed the meat of native animals or other “bush tucker”. He was diffusely thin and weak, with bilateral incomplete foot drop and depressed reflexes, but intact facial strength and normal ocular movements. The serum CK level was 1230 U/L and, in retrospect, had been 1000 U/L 2 years earlier, but had not been investigated. Alanine aminotransferase was 69 U/L (RR, < 45 U/L); aspartate aminotransferase, 67 U/L (RR < 40 U/L); and peripheral blood eosinophils, 1.36 × 109/L (RR, < 0.4 3 109/L). Review of earlier investigations confirmed persistent eosinophilia over the prior 42 months, at least. Muscle biopsy confirmed H. perplexum. He received 8 weeks’ oral treatment with albendazole. Steroids were not given. Four months later there was some improvement in limb strength and swallowing, although his CK level remained high. DiscussionAlthough H. perplexum myopathy has previously been reported, in two people from Tasmania,1,2 the patients we report had spent most or all of the past few years in tropical northern Australia. We contacted the physicans caring for the earlier patients, who confirmed that they, too, had been exposed to tropical Australia (Box 4). One had travelled extensively in Cape York, Far North Qld, and Kakadu National Park, Northern Territory, 5 years before diagnosis. Around that time, he developed a non-specific illness with raised liver transaminase levels, and liver biopsy showed mild reactive hepatitis with eosinophils. The other was a botanist who had visited the Northern Territory, Tasmania, Europe, Kenya and Indonesia on fieldwork before developing muscle weakness. Clinical features common to H. perplexum myositis patients were the insidious onset of diffuse limb weakness and dysphagia. The documentation of persistent eosinophilia up to 7 years before diagnosis suggests that infection may be subclinical for years. Consistent clinical signs have been diffuse limb wasting and weakness, including bilateral foot drop. Uniform abnormalities included an elevated serum CK, blood eosinophilia and mild elevations of liver transaminases. Although muscle biopsy is required to confirm diagnosis, in one reported case the initial biopsy did not reveal parasites, but a second biopsy after steroid treatment showed H. perplexum. H. perplexum is a minute nematode measuring about 350 m by 20 m. The parasite appears to be able to complete its life cycle within human muscle, as adult nematodes are found within the sarcoplasm of muscle cells, while larvae are found both inside and outside myofibres.3 Electron microscopy shows the characteristic features of H. perplexum: a cuticularised triradiated oesophagus–intestine terminating in dark refringent granules (trophosomes).1 The outer cuticle is thin and has exterior corrugations. The male is shorter and narrower than the female, with the testes occupying 50%–60% of its body. The gravid female has paired uteri where 12 to 24 ova develop into larvae. Auto-reinfection is thought to occur when third-stage larvae escape by bursting through the female nematode’s body, a phenomenon known as endotokia matricida. The resulting damaged myofibres incite an intense inflammatory reaction resulting in myophagia. H. perplexum was first described in the late 1990s, having been identified as the cause of a case of human myositis.2 The parasite is a member of the Robertdollfusidae family of Muspiceoidea nematodes. Distinct species of Muspiceoidea nematodes have been found in the tissues of various Australian vertebrates,4 including mice,3 bats,5 kangaroos and wallabies,6 and koalas.7 In animals, there is some evidence for cutaneous penetration as the mechanism of infection.3 The mechanism by which humans acquire H. perplexum is unknown. Other parasitic myopathies such as trichinosis and cysticercosis are acquired through consumption of poorly cooked meats. Intestinal parasites, including Strongyloides, may be acquired via direct cutaneous penetration, such as when walking barefoot, a common practice in tropical Australia. Mosquitoes, which are very common in tropical Australia during the wet season, could also be a vector for infection. Treatment with albendazole improved muscle strength in all three cases of H. perplexum myopathy, although recovery was slow and incomplete. A biopsy after 4 weeks of treatment showed live nematodes. After 9 weeks of treatment, no live nematodes were seen on biopsy, correlating with a reduction in CK levels and peripheral eosinophilia. Therefore, treatment for at least 8 weeks is suggested to prevent auto-reinfection. Treatment solely with albendazole, without concomitant steroid use, was not associated with adverse reactions from nematode death. Furthermore, steroid therapy resulted in deteriorating muscle function and delayed diagnosis by falsely normalising blood eosinophilia. 1 A 23-year-old woman with progressive muscle weakness (Patient 1) The patient had diffuse wasting of major lower limb muscle groups, including the quadriceps. The white arrow shows wasting of the tibialis anterior muscle, which caused foot drop. The black arrow shows the well preserved digitorum brevis muscle, accounting for preserved toe extension. 2 Micrographs of skeletal muscle (Patient 1) A: Transverse section of quadriceps muscle fibres (M) shows a nematode, Haycocknema perplexum (HP), in cytoplasm, surrounded by interstitial chronic inflammatory cells (INF) (haematoxylin and eosin stain; original magnification, × 400). B: Longitudinal section shows parasitic nematode lying within the muscle fibre (toluidine blue stain; original magnification, × 1000). 3 Electron micrographs of Haycocknema perplexum nematode A: Cross-section through nematode in skeletal muscle (M), showing cuticle (Cu) and oesophagus (O) (original magnification, × 2500). B: Enlargement shows cuticularised triradiated lumen of the oesophagus (original magnification, × 20 000). 4 Clinical and laboratory features of myopathy caused by Haycocknema perplexum Patient Place and year of diagnosis Prior travel Duration of symptoms (years) Dysphagia CK level (U/L)* Eosinophil count (× 109/L)† Outcome 1 North Qld, 2005 Extensive 2 ++ 1370 1.1 Weak, CK ~ 300 U/L 2 North Qld, 2004 None in 20 years 3 ++ 1263 High Weak, died 3 North Qld, 2006 Nil 2 + 1230 1.36 Weak, CK ~ 250 U/L Previously reported cases2 A Tasmania, 1996 Extensive, including Far North Qld 1.5 ++ 1586 2.0 Weak, CK ~ 280 U/L B Tasmania, 1994 Extensive, including northern Australia 5 + 2168 0.8 Good recovery CK = creatine kinase. Qld = Queensland.+ = mild–moderate. ++ = moderate–severe. * Reference range (RR), < 160 U/L. † RR, < 0.4 3 109/L.

Ron Basuroy MRCP · Robert Pennisi FRACGP · Thomas Robertson FRCPA · Robert Norton FRCPA, MRCP · John Stokes FJFICM · Jon Reimers FRACP · John Archer FRACP, PhD

Roman Rossleigh, a caring physician, committed family man and community-minded citizen, died of multiorgan failure on 14 September 2007 after a long battle with chronic illness. Roman was born on 13 October 1919 in Kraków, Poland. His mother, a dermatologist, treated venereal diseases in women, and his father, a cardiologist, trained under Karel Wenckebach. When the Nazis invaded Poland, Roman was tortured, resulting in bilateral brachial plexus palsies and a left hemiparesis, which worsened over the years. He was incarcerated in Plaszów and then Mauthausen concentration camps and liberated on 5 May 1945 — a day he celebrated in later years as his “re-birthday”. He became a fourth generation physician after World War II, completing his medical degree in Lódz in 1946. He met his future wife Christine in the same year, fell madly in love, and married her after they had known each other for only 3 days. Their marriage lasted 61 years. Roman migrated to Australia in 1947, studied medicine again at the University of Sydney, and became registered as a medical practitioner in 1952. He was proud to have been able to maintain his medical registration until the end of his life. In 1974, he was awarded Fellowship of the Royal Australian College of General Practitioners, and several years ago was recognised for his 50-year membership of the Australian Medical Association. Practising in Newtown, Sydney, Roman had many migrant patients, owing to his reputation as a good doctor and his ability to speak seven languages. He was a member of the New South Wales Association for Mental Health and was on the committee for migrant mental health. He was a strong advocate for the establishment of an interpreter service, which is now widely used throughout the NSW health system. He opposed the use of children as interpreters for their parents because of the often sensitive nature of the problems discussed and the potential for mental harm to the children. Roman was actively involved in the affairs of the Polish community in Australia, for which he was recognised by the Polish Government with the award of several medals, including the Knight Cross of the Order of Merit of the Republic of Poland (an award analogous to the Order of Australia). He was a Freemason, a strong supporter of many charities and a lover of books, history, music, travel and ball sports — in particular, football (soccer) and cricket. Roman is survived by Christine, his daughter Monica, a nuclear medicine physician, and son Martin, a school teacher.

Monica A Rossleigh

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

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

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

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

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

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

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

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

Chlamydia screening programs overseas have failed to reduce chlamydia prevalence despite screening 20%–30% of young sexually active women. The Australian federal government announced in 2005 that it would provide $12.5 million for chlamydia control. Policymakers must look to chlamydia screening programs in other countries to learn from their experience. Australia has an excellent primary health care system and a strong track record in establishing highly successful public health programs. This experience places it in a strong position to design and implement an innovative chlamydia screening program to reduce chlamydia prevalence.

Jane S Hocking MPH, MHthSc(PHP), PhD · Jennifer Walker BAppSc, MPH · David Regan BSc(Hons), PhD · Marcus Y Chen MRCP, FAChSHM, PhD · Christopher K Fairley PhD, FAFPHM, FACSHP

Hand hygiene should be the highest priority In this issue of the Journal there is yet another article showing that methicillin-resistant Staphylococcus aureus (MRSA) can easily be found on environmental surfaces — this time on identity badges and lanyards (→ What's hanging around your neck? Pathogenic bacteria on identity badges and lanyards).1 This adds to an increasing array of items such as neckties, stethoscopes, pens, computer keyboards and coats that can be colonised by pathogenic bacteria (although usually only in low numbers). While it is helpful to know all the places we may find MRSA, these types of studies really just confirm what should be blindingly obvious — that MRSA readily disseminates within our health care environment. Thus, the hands of health care workers will frequently come into contact with MRSA. The real issue with the control of MRSA is not the need for more information on environmental contamination, but the need to use the abundant information we already have to curtail the principal way that MRSA spreads in hospitals — via the hands of health care workers.2-4 Our inability to adequately address the key issues2 means that, increasingly, others will intervene, sometimes with mistaken emphasis and priorities. The United Kingdom has just mandated a “bare below the elbows” dress code in its hospitals.5 This means no more coats or even wristwatches, despite a lack of evidence that these items play a major role in transmitting MRSA. The UK Prime Minister has called for better cleaning of wards, in the belief that this is the key to controlling MRSA.5 While there is some merit in these proposals, they are focusing on elements that are minor compared with the most important one — how best to stop MRSA spreading via hands. We already know more than enough to control MRSA.2 If we use regular hand hygiene procedures with alcohol/disinfectant solutions we can reduce serious infections caused by MRSA. Better screening policies will identify people carrying MRSA and help to keep them away from those not already carrying the organism. If we wear appropriate gowns and gloves when dealing with patients (especially those known to have MRSA), then clothing and other inanimate articles will less often become contaminated with MRSA. Having more single rooms in hospitals and reducing overcrowding in emergency departments and other areas will make it easier to separate patients with MRSA from those without. We need to follow “isolation” rules, such as preventing staff from bringing their own stethoscopes or other equipment into a room where a patient with MRSA is being cared for. If we use hand hygiene procedures before and after seeing each patient, even if our hands have been in contact with MRSA on an inanimate surface, any MRSA organisms should be killed before our hands transmit them to patients. The question is, how do we change our current work practices and behaviour to ensure that these important elements are followed, not just some of the time but all the time? We don’t need more environmental-type studies without clinical endpoints. We need studies in which we intervene and show that the interventions reduce the number of people infected with MRSA.3,4 Surprisingly, there are few such studies, which is likely a reflection of how we regard quality improvement (QI) programs. QI research is not “sexy”. It is often difficult to attract funding for QI studies and get them published, because the realities of clinical practice mean that it is frequently hard to control all variables. Nevertheless, it is peer-reviewed QI programs with successful interventions that are most likely to lead to long-term reductions in MRSA infections. MRSA is a major and increasing problem worldwide. Unfortunately, the extent of infections caused by MRSA is not measured consistently or accurately (and often not at all). Timely data are not readily available for the vast majority of Australian hospitals. In England, it was mandated in April 2001 that all MRSA bacteraemia episodes be notified.6 Data from individual hospital trusts are now accessible on the Internet.7 While making the data available has generated disagreements,8,9 this intervention coincided with the first sustained year-by-year fall in the number of MRSA bacteraemia episodes (from 7700 in 2003–04 to 6378 in 2006–07). In Australia, over 4500 episodes of health care-related S. aureus bacteraemia occur per year.10 Of those, about 2000 episodes involve MRSA, with a 35% mortality rate. We need the health care profession to better define the extent of disease caused by MRSA and other serious pathogens using practical and robust outcome measures.7,11 Data from a broad range of institutions need to be made available to enable meaningful comparisons, so that institutions with higher rates of infection can learn from their colleagues with lower rates. Hospital managers need to be part of this process. We also need to ensure that we not only measure what is going on, but, more importantly, do something about it.11 It is possible for us to achieve much better control of MRSA. Denmark, The Netherlands and Western Australia, for example, have kept the number of health care-acquired MRSA infections down to low levels.2 We know what the problem is. What we appear to lack is an understanding of human behaviour and the political and medical will to really do something about it. It is time to change. We have been missing the big picture for too long.

Peter J Collignon FASM, FRCPA, FRACP

Objective: To determine whether identity badges and lanyards worn by health care workers (HCWs) are capable of harbouring potentially pathogenic bacteria.Design, setting and participants: Cross-sectional study of 71 HCWs (59 clinical ward staff and 12 infection control staff) at Monash Medical Centre, a university teaching hospital. Samples from lanyards, identity badge surfaces and connections (eg, clips, keys, pens) were cultured. The study was conducted from July to August 2006.Main outcome measures: Presence of pathogenic bacteria on identity badges and lanyards; differences in bacterial counts on items carried by nurses and doctors.Results: A total of 27 lanyards were identified with pathogenic bacteria, compared with 18 badges. Analysing lanyards and badges as a combined group, seven had methicillin-resistant Staphylococcus aureus, 29 had methicillin-sensitive S. aureus (MSSA), four had Enterococcus spp and five had aerobic gram-negative bacilli. Lanyards were found to be contaminated with 10 times the median bacterial load per area sampled compared with identity badges. There were no significant differences between nurses and doctors in total median bacterial counts on items carried, but doctors had 4.41 times the risk of carrying MSSA on lanyards (95% CI, 1.14–13.75).Conclusion: Identity badges and lanyards worn by HCWs may be contaminated with pathogenic bacteria, which could be transmitted to patients. In view of this finding we suggest appropriate infection control interventions.

Despina Kotsanas BSc(Hons), MClinEpi · Carmel Scott BN · Elizabeth E Gillespie BN, MPubHealth · Tony M Korman MB BS, FRACP, FRCPA · Rhonda L Stuart MB BS, FRACP, PhD

We report eight recent cases of Chikungunya virus infection in travellers to Australia. Patients presented with fevers, rigors, headaches, arthralgia, and rash. The current Indian Ocean epidemic and Italian outbreak have featured prominently on Internet infectious disease bulletins, and Chikungunya virus infection had been anticipated in travellers from the outbreak areas. Diagnosis was by a generic alphavirus reverse transcriptase polymerase chain reaction with confirmatory sequencing. Prompt diagnosis of Chikungunya virus infections is of public health significance as the mosquito vectors for transmission exist in Australia. There is potential for this infection to spread in the largely naïve Australian population.

Douglas F Johnson MB BS(Hons) · Julian D Druce BSc, MSc · Scott Chapman MB BS, FRACP · Ashwin Swaminathan MB BS · Josh Wolf MB BS · Jack S Richards MB BS, FRACP · Tony Korman MB BS, FRACP, FRCPA · Chris Birch BSc, MSc, PhD · Michael J Richards MB BS, MD, FRACP

To the Editor: The report by Risson and colleagues of a fatal case of necrotising pneumonia caused by community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA)1 appropriately highlights the emerging issue of CA-MRSA infections in Australia,2 and the possibility that severe S. aureus sepsis may follow recurrent furunculosis. We wish to draw attention to the association between severe staphylococcal pneumonia and a preceding influenza-like illness. In September 2006, a 56-year-old woman of European background with a history of chronic back pain and depression presented to the Royal Darwin Hospital after a 4-day influenza-like illness characterised by cough, fever and sore throat. She then developed dyspnoea and pleuritic chest pain, followed by an abrupt respiratory deterioration. She was intubated and admitted to the intensive care unit with severe sepsis. A chest x-ray showed widespread bilateral pneumonia. We began broad-spectrum antibiotic therapy with piperacillin–tazobactam and azithromycin as per the hospital’s dry-season protocol for severe community-acquired pneumonia. Further history from her husband revealed an episode of boils 1 month previously, which responded to antibiotic therapy. We added vancomycin to the therapy and, when sputum and blood cultures showed MRSA 48 hours after admission, we also added rifampicin and gentamicin. On Day 5 of admission, her clinical condition deteriorated further and we replaced rifampicin and gentamicin with linezolid. Complement fixation testing of serum taken on admission showed an influenza A antibody titre of 128, consistent with recent acute infection. Despite ongoing intensive supportive care, the patient died from refractory respiratory failure 10 days after admission. Typing of the S. aureus isolates from blood and sputum showed that their single nucleotide polymorphism and variable gene profile was consistent with the Queensland clone (ST93-MRSA-IV) of CA-MRSA, and that the Panton–Valentine leukocidin gene was present. S. aureus has long been a recognised cause of influenza-associated pneumonia. Of concern, two recent reports from the United States identified 25 patients with CA-MRSA associated with severe pneumonia following influenza-like illnesses.3,4 Most of these patients were young (median age of 21 years3 and 17.8 years,4 respectively) and otherwise healthy. Combined mortality in these two studies was 40%. With an increasing prevalence of CA-MRSA in areas of Australia,2 CA-MRSA pneumonia should be suspected in patients presenting with worsening respiratory status and sepsis following an influenza-like illness. We stress the importance of annual influenza vaccination for those at increased risk of influenza-related complications.5

Steven Y C Tong · Nicholas M Anstey · Gary D Lum · Rachael A Lilliebridge · Dianne P Stephens · Bart J Currie

To the Editor: The recent editorial by Collignon and colleagues emphasised the importance of infection control mechanisms in reducing patient harm from antibiotic-resistant organisms.1 It focused on disinfection of the hands of health care workers in hospitals. However, a vigorous education and surveillance program in a hospital in Victoria failed to achieve compliance among health care workers of even 50%.2 Top of the list of self-reported factors leading to poor compliance is “skin irritation and dryness associated with the use of hand hygiene agents”.3 There have been no properly controlled trials, with clinically important endpoints, of currently recommended hand-hygiene practices. With the likely poor compliance rates, such trials would likely fail. A different approach might be more effective. Reducing skin contact between health care workers, patients and their immediate environment seems logical. Data show that skin contact produces two-step transfer of material in 82% of cases.4 The Victorian study did include gloving as an alternative to disinfection in measuring hand-hygiene compliance.2 However, in what might be a backward step, a recent study concluded that physicians should be encouraged to shake hands with patients!5 Perhaps an educational campaign to avoid skin contact with environmental surfaces and other health care workers, with use of disposable gloves for patient contact, could be the basis of a successful trial to address more effectively the transmission of antibiotic-resistant organisms in hospitals.

Keith V Woollard

To the Editor: The magnitude and distribution of the problem of health care-associated methicillin-resistant Staphylococcus aureus (MRSA) in Australia can be gauged from the report of a forum on MRSA control conducted at the Australasian Society for Infectious Diseases (ASID) in March 2007.1 This report contrasted approaches to control of health care-associated MRSA and quantified the population incidence rate of health care-associated MRSA bacteraemia across Australia from data derived from direct surveillance systems (Box). Reporting of MRSA infections is thought to be complete from all jurisdictions except Victoria and New South Wales. Figures for Victoria were extrapolated from accurate surveillance data representing 50%–60% of events. The degree of incompleteness of reporting in NSW could not be determined, and a range based on reports to NSW Health over 3 years was used. Overall morbidity of health care-associated MRSA in Australia is much higher, as only a minority of MRSA infections lead to bacteraemia. The ASID report estimated that between 699 and 924 cases of bacteraemia would be prevented if other states and territories reduced their incidence of MRSA bacteraemia to that of Western Australia through implementation of more stringent infection control measures. The mortality of MRSA bacteraemia is 8%–50% (average, 29%).2 A recent study showed that more than half (59%) of such deaths were directly attributable to MRSA3 rather than other non-infective causes. These outcome proportions provide a minimum estimate of between 120 and 158 preventable deaths per annum in Australia directly caused by health care-associated MRSA — comparable to the annual South Australian road toll. As identified recently in the Journal by Collignon and colleagues, there are significant structural barriers to achieving infection control — especially inadequate isolation resources and pressure on bed stock.4 Other dimensions of the MRSA problem include the high incidence of MRSA in many aged care facilities, the epidemic emergence of community strains of MRSA (best described in the recent report from WA on MRSA notification data up until 20025), the possibility of significant zoonotic reservoirs,6 and the role played by imprudent antibiotic use. MRSA colonisation or infection needs to be made a nationally notifiable disease, with a system in place to enable typing of isolates. As in WA, such a system would enable more effective identification of MRSA carriers before hospital admission, the detection of emerging epidemic strains, and timely investigation of MRSA outbreaks occurring in community groups, such as in aged care facilities. Most importantly, all states and territories need to adopt, and provide resources for, consistent, stringent approaches to surveillance, prevention and control of health care-associated MRSA that are in keeping with internationally recommended approaches. Given the scale of preventable injury occurring in many states, MRSA control must be made one of the highest priorities for patient safety. Relative burden of health care-associated MRSA morbidity across Australia1 Area Health care-associated MRSA bacteraemia events Year(s) of data Rate per 100 000 population Darwin 16 2006 13.3 New South Wales/ACT*† 437–602 2003–2005 6.2–8.5 Queensland* 133 2005 3.4 South Australia* 37 2006 2.4 Tasmania* 3 2006 0.6 Victoria*† 270–330 2000–2006 5.4–6.6 Western Australia* 22 2006 1.1 Total 918–1143 4.5–5.7 MRSA = methicillin-resistant Staphylococcus aureus. ACT = Australian Capital Territory. * Figures from these jurisdictions include private hospital event estimates. † Figures from NSW and Victoria are minimum estimates, because of incompleteness of current reporting in these states.

John K Ferguson · Helen Van Gessel