Infectious diseases

What can we do to prevent this from becoming the most common health care-associated infection in Australia? Clostridium difficile, a gram-positive, anaerobic, spore-forming, toxigenic bacterium, is the most common infectious cause of nosocomial diarrhoea. The severity of infection varies from mild diarrhoea to pseudomembranous colitis, toxic megacolon and death.1 In the United States, C. difficile now rivals methicillin-resistant Staphylococcus aureus (MRSA) as the most common health care-associated infection, accounting for US$3.2 billion in excess costs annually.1,2 Since 2000, there has been an increase in the rates of C. difficile infection (CDI) in some health care facilities in the US, Canada and Europe, associated with an epidemic strain of C. difficile. This strain (B1/NAP1/027, toxinotype III or PCR ribotype 027) is characterised by its increased resistance to fluoroquinolones, increased toxin production (toxins A, B and binary toxin), increased sporulation, and increased morbidity and mortality.1,3 Risk factors for CDI include exposure to antimicrobial drugs, gastric acid-suppressive therapy, advanced age, prolonged hospitalisation, cancer chemotherapy, comorbidity and immunosuppression.3 Although most cases have been in hospital inpatients, increasing numbers of community-associated cases are now being reported in the US and Europe.4,5 Australia is now also in the grip of this new strain of C. difficile. The first infected patient was reported in 2009 in Western Australia, but the infection was thought to have been acquired in North America.6 In this issue of the Journal, Richards and colleagues report the first case of C. difficile ribotype 027 thought to have been acquired in Australia (→ Severe infection with Clostridium difficile PCR ribotype 027 acquired in Melbourne, Australia).7 The strain was identified after clinicians alerted the laboratory to the severity of the infection and the possibility of a hypervirulent strain. Since this case was first reported, there have been further clusters of C. difficile ribotype 027 infection centred around residential aged care facilities. Currently, surveillance for C. difficile is not consistent across Australia, so rates of CDI across the continent are unknown. However, some states have commenced surveillance and show overall rates varying between 1.27 and 2.3 CDIs per 10 000 bed-days.8 This contrasts with a reported overall rate in Canada of around 3.8–9.5 CDIs per 10 000 bed-days based on surveys conducted in 1997 and 2005.9 Clinicians need to be aware of the clinical picture, diagnostic methods and new therapeutic approaches to this disease. The Australasian Society for Infectious Diseases has published guidelines in this issue of the Journal that clearly outline clinical assessment, diagnostic issues and treatment guidelines (→ Australasian Society for Infectious Diseases guidelines for the diagnosis and treatment of Clostridium difficile infection).10 Identification of hospitalised patients with CDI is the key to preventing transmission. Hospitals need to have an optimal surveillance program in place to expedite patient testing and identification. As a minimum standard, all patients with hospital onset of diarrhoea (> 48 hours after admission) should be screened for CDI. The case definition for CDI should include: (i) symptoms (usually diarrhoea); and (ii) a stool test positive for toxigenic C. difficile or its toxins, or colonoscopic or histological findings of pseudomembranous colitis.9 Similarly, clinicians working in residential aged care facilities need to be alert to the possibility of CDI in residents, to undertake testing in the presence of symptoms and to focus on decreasing transmission of the infection within the facility. In the hospital setting, infection control precautions around cases of CDI need to be enforced. Infection control guidelines for CDI from the Australasian Society for Infectious Diseases and the Australian Infection Control Association have recently been released.11 The main management principles for control of CDI include: all health care organisations, including residential aged care facilities, giving CDI prevention and control the highest priority, even if the prevailing incidence of CDI is low; surveillance being integrated into quality improvement programs to optimise prevention and control of CDI and clinical care of infected patients; antimicrobial stewardship programs being in place that are aimed at minimising the frequency and duration of antibiotic use and promoting a narrow-spectrum antibiotic policy; emphasis on compliance with hand disinfection and glove use for care of patients with CDI to minimise spore contamination; contact precautions being employed for symptomatic patients with CDI, including the donning of gowns or aprons and gloves on entry to patient rooms; use of sporocidal environmental cleaning and disinfection in high-risk areas such as toilets, bathrooms and rooms of patients with CDI, and elimination of other potential fomites by either using disposable equipment or ensuring that equipment is adequately cleaned and disinfected before reuse; and education of all health care staff, patients and visitors about CDI, its prevention and management. It is sobering to contemplate that what has occurred in the US, Canada and Europe is potentially and imminently on our doorstep. We must learn from the experience of experts in these countries so that Australia can avoid a similar experience — we already have the benefit of their hindsight to guide us. Our challenge is implementing the necessary interventions — enhanced surveillance and diagnosis, antimicrobial stewardship, environmental cleaning and stringent infection control. Although this solution re-echoes the usual infection control mantra, it is essential that we act pre-emptively to prevent CDI from occurring, especially to the most vulnerable of our patients.

Rhonda L Stuart MBBS, FRACP, PhD · Caroline Marshall FRACP, PhD, GradDipClinEpi

Clostridium difficile is the most common cause of health care-associated and antibiotic-associated diarrhoea. These guidelines are intended to provide advice to clinicians on the clinical assessment, diagnosis and management of C. difficile infection (CDI). Hypervirulent strains of C. difficile, including PCR ribotype 027 strains recently identified in Australia, have been associated elsewhere with epidemic spread and high rates of severe disease and death. Diagnostic tests include stool culture, polymerase chain reaction-based assays, cell-culture cytotoxicity assays and enzyme immunoassays detecting C. difficile glutamate dehydrogenase, and/or toxin A and/or B. To treat an initial episode and a first recurrence, metronidazole is the preferred antibiotic, with oral vancomycin reserved for severe disease and subsequent recurrences. Surgery should be considered for fulminant disease.

Allen C Cheng FRACP, MPH, PhD · John K Ferguson FRACP, FRCPA, DTMH · Michael J Richards MB BS, FRACP, MD · Jennifer M Robson FRACP, FRCPA, FACTM · Gwendolyn L Gilbert MD, FRACP, FRCPA · Alistair McGregor MB BS, FRACP · Sally Roberts MB ChB, FRACP, FRCPA · Tony M Korman MB BS, FRACP, FRCPA · Thomas V Riley MAppEpid, PhD, FRCPath

Frank Fenner was one of Australia’s greatest scientists, internationally recognised for his research into viral diseases and for his achievements in the eradication of smallpox and the control of Australia’s rabbit plague. He was born in Ballarat on 21 December 1914, the second son of Emma and Charles Fenner. After schooling in Adelaide, he studied medicine at the University of Adelaide, graduating in 1938. As a university student, he gained his Blue in hockey, presaging a lifetime of participation in sport and a love of tennis. In 1940, he joined the Australian Army Medical Corps, serving in the Middle East, New Guinea and Borneo. His Army service was predominantly as a malariologist, reflecting his studies in tropical medicine. At Hughenden Hospital in Queensland, he treated servicemen and women returning from Papua New Guinea with malaria, and it was there that he met and married Bobbie Roberts in 1943. Fenner’s extensive achievements in controlling malaria were recognised in 1944 when he was made a Member of the Order of the British Empire. Fenner joined the Walter and Eliza Hall Institute in Melbourne in 1946, working with Sir Frank Macfarlane Burnet. A landmark achievement was their publication of The production of antibodies (2nd edition. Melbourne: MacMillan, 1949), in which they proposed that the exposure of a young, immature animal to foreign cells or tissues would confuse the animal’s immune system into regarding other foreign transplants from the same source as “self”. Fenner’s laboratory research at the Institute focused on mousepox. This work would lead to his commitment to ridding the world of smallpox a quarter of a century later. In 1949, he was appointed Foundation Professor of Microbiology at the John Curtin School of Medical Research (JCSMR) at the Australian National University (ANU) in Canberra. His first major research there was on using myxomatosis to biologically control the rabbit plague that was wreaking havoc on Australian farming land. The introduction of the myxoma virus into the rabbit population coincided with an outbreak of encephalitis in the Murray–Darling basin. Perceptions that the two events were associated gained currency and, in one of the legendary episodes in the history of Australian epidemics, Fenner and two colleagues inoculated themselves with the myxoma virus to successfully refute that association. The relevance of Fenner’s work on myxomatosis has increased over time, with the emergence of diseases such as AIDS, variant Creutzfeldt–Jakob disease and severe acute respiratory syndrome, which are caused by agents that have crossed from other species rather than coevolving with human hosts. Fenner’s research progressed to another pox virus, vaccinia or cowpox, which was used clinically in vaccination against smallpox. His growing reputation in the 1950s was reflected in his election as a Fellow of both the Australian Academy of Science and the Royal Society. Further recognition of his scientific standing came in the 1960s with a Leeuwenhoek lectureship of the Royal Society and a Britannica Australia award. In 1967, he left bench for books to become the first Director of the JCSMR. His most notable publications were The biology of animal viruses (New York: Academic Press, 1968) and Medical virology (New York: Academic Press, 1974). His experience with pox viruses led to an invitation to join an international scientific project to eliminate smallpox and, in 1977, to his appointment as Chairman of the Global Commission for Certification of Smallpox Eradication. He later nominated 8 May 1980, when he announced the eradication to the World Health Assembly, as the proudest day of his life. Fenner’s environmental interests underpinned his appointment as founding Director of the Centre for Resource and Environmental Studies at the ANU in 1973. They also found expression in his roles as Vice President of the Australian Conservation Foundation (1971–1973) and as a member of the Senior Scientific Advisory Board of the United Nations Environment Programme. During this period, recognition of his achievements included being made a Companion of the Order of St Michael and St George in 1976, followed in 1977 by election as a foreign associate of the United States National Academy of Sciences. On retirement in 1979, he returned to the JCSMR to work with undiminished intensity. Perhaps the most visible aspect of his retirement was the succession of awards he received. Among these were the 1980 Anzac Peace Prize, the 1988 Japan Prize, being made a Companion of the Order of Australia in 1989, the Copley Medal of the Royal Society in 1995 and the Prime Minister’s Prize for Science in 2002. He wrote a number of books dealing with historical aspects of science and was coauthor of the encyclopaedic Smallpox and its eradication (Geneva: World Health Organization, 1988). In an instructive illustration of the durability of scientific knowledge, more than 20 years after his nominal retirement he was advising national expert groups on the potential for pox viruses in bioterrorism. As well as his more widely publicised achievements in retirement, his philanthropy and his unstinting accessibility to academics and students were notable. As a Visiting Fellow at the JCSMR, he represented a repository of information on virology. If he did not have the required information at his fingertips, he could invariably tell one exactly where it could be found. Frank Fenner died on 22 November 2010 after being admitted to hospital with septicaemia. He is survived by his daughter Marilyn.

Peter McCullagh

We report the first recognised case of infection with Clostridium difficile PCR ribotype 027 acquired in Australia. This pathogen has caused significant morbidity and mortality in widespread hospital-based outbreaks in the northern hemisphere. Clinicians need to be aware of the clinical picture, limitations of diagnostic tests, availability of further testing for epidemic strains, new therapeutic approaches, and in-hospital control strategies for this infection. (MJA 2011; 194: 369-371) Clinical recordAn 83-year-old Latvian man underwent an aortic valve replacement for aortic stenosis in late January 2010 at a hospital in Melbourne, Australia. He had a history of hypertension and chronic renal failure. He lived alone in his own home, and had not travelled outside Australia since September 2009 when he returned from a 3-month trip to Latvia. Between his return to Australia and the surgery, he had not received any antibiotics except for a single preoperative dose of cephalothin. His regular medications included various supplements, but no proton-pump inhibitor. He was admitted to the hospital the day before surgery. Two days after the surgery, he developed severe sepsis from a urinary tract infection, for which he received ticarcillin–clavulanate and a noradrenaline infusion. A coagulase-negative Staphylococcus was isolated from blood cultures, and he was given vancomycin. He later developed an infiltrate at the left lung base, but no change was made to his therapy. Five days after the surgery, he developed watery diarrhoea. Clostridium difficile was isolated from stool samples, although the results of enzyme-linked fluorescent assays (VIDAS, bioMérieux, Sydney, NSW) for C. difficile toxins were negative at this time. His leukocyte count was 9.5 × 109/L (reference range, 4.0–11.0 × 109/L) and his serum albumin concentration was 42 g/L (reference range, 35–50 g/L). Therapy with metronidazole (400 mg orally, 8-hourly) was commenced for presumed C. difficile infection (CDI), and the patient was placed under contact precautions. Alcohol-based hand rub was replaced with traditional soap and water hand washing (see below). Therapy with ticarcillin–clavulanate was subsequently ceased. After 9 days of metronidazole therapy, the diarrhoea became more frequent and vancomycin (250 mg orally, 6-hourly) was substituted. Repeat stool specimens were tested. This time, C. difficile toxins were identified by enzyme-linked fluorescent assay, and C. difficile was isolated again. Because of the patient’s deteriorating condition, the laboratory was alerted to the possibility of a hypervirulent strain. The isolate was tested for susceptibility to moxifloxacin (Etest, bioMérieux, Sydney, NSW) and found to be resistant, with a minimum inhibitory concentration of > 32 μg/L. The stool sample was positive by real-time polymerase chain reaction (PCR; GeneXpert, Cepheid, Sunnyvale, Calif, USA) when tested for the presence of C. difficile organisms carrying genes for toxin B (tcdB), binary toxin (cdtB) and an 18-base-pair deletion within the tcdC gene that is characteristic of the PCR ribotype 027 strain. These findings were confirmed by sequencing the tcdC gene, and this also identified a point mutation at nucleotide position 117, which is also characteristic of this strain. PCR ribotyping was undertaken using a previously published method1 that confirmed the isolate as PCR ribotype 027 (Box). Nineteen days after surgery, the patient’s condition deteriorated further. His temperature was 39.2°C, his leukocyte count was 31.2 × 109/L and his serum albumin concentration was 25 g/L. The diarrhoeal frequency fell to a single bowel action per day, and an abdominal x-ray showed a distended right colon. The oral vancomycin dose was increased to 500 mg, 6-hourly, and therapy with intravenous metronidazole was commenced along with vancomycin enemas (500 mg in 500 mL normal saline, 6-hourly). Ticarcillin–clavulanate therapy was recommenced. A surgical opinion was sought and subtotal colectomy discussed. As there was felt to be a high risk of mortality with surgery, medical management was preferred. After 5 days, the fever and diarrhoea improved. The enemas were ceased after 8 days and metronidazole therapy after 14 days. The patient subsequently recovered, and the diarrhoea had not recurred at 3-month follow-up. DiscussionAn epidemic strain of C. difficile (PCR ribotype 027) was first identified in Quebec Province in Canada in 2005, as a cause of hospital outbreaks of severe infection with high mortality rates.2 Retrospective analyses suggested that this strain had caused outbreaks across North America since 2000.3 The organism later spread to Europe, and cases have now been described in Asia and Central America.4 Increased toxin production by C. difficile PCR ribotype 027 may be responsible for its increased virulence,5 and fluoroquinolone resistance is likely to be contributing to its spread.6 Infection with this strain more often leads to severe disease, and is associated with more recurrences and a greater risk of death.2 Until now, only one case has been described in Australia in a patient who was thought to have acquired the infection in North America.7 This is the first case of hypervirulent CDI diagnosed in Australia with apparent local acquisition. Several factors support the conclusion that the infection was not acquired overseas. First, although the patient had travelled to Latvia 4 months before being admitted, the possibility that he acquired C. difficile PCR ribotype 027 then and remained colonised is remote. C. difficile does not colonise the normal adult gastrointestinal tract, and the patient received no antibiotics that may have disrupted his gut flora in the time between returning from Latvia and admission to hospital. Second, a recent publication from Latvia indicates that C. difficile ribotype 027 was not present in the country when our patient was there.8 Finally, there were at least two other subsequently confirmed cases of infection with C. difficile PCR ribotype 027 in the hospital at the time the patient developed symptoms of infection (it is not known where these cases were acquired). The case illustrates important features of hypervirulent CDI. The identification of severe disease is critical in guiding management. For surveillance purposes, severe disease may be simply identified as infections requiring ICU admission or surgery, or infections resulting in death, or a diagnosis of toxic megacolon.9 More sensitive diagnostic criteria for severe disease in addition to those above are required to guide patient care. While no such criteria have yet been prospectively validated, proposed markers of severe disease include age greater than 65 years, leukocytosis greater than 20 × 109 cells/L, deterioration of renal function, temperature greater than 38.3°C, serum albumin concentration less than 25 g/L and an elevated serum lactate concentration.10 Our patient met all these criteria except for the serum lactate concentration, which was not recorded. Although metronidazole remains the recommended first-line agent for mild to moderate CDI, oral vancomycin is now recommended for severe disease.9,10 Although there is no evidence that high-dose oral vancomycin (500 mg, 6-hourly) is any better than standard doses of 125 mg 6-hourly, higher doses are favoured by many clinicians. Evidence of benefit for vancomycin enemas is limited to case series; eight of nine patients with refractory severe disease had complete resolution with this therapy.11 In the setting of ileus with toxic megacolon, oral vancomycin will not reach the colon and intravenous delivery of metronidazole is preferable.12 Surgery should be considered if severe disease is unresponsive to medical therapy after 48 hours, or if there is bowel perforation or multiorgan failure.13 Elevation of plasma lactate to between 2.2 and 4.9 mmol/L has been identified in a retrospective review of a selected group of severely ill patients as a guide to when colectomy is most beneficial.14 Other strategies requiring further investigation for use in severe disease include intravenous immunoglobulin, alternative antibiotics such as tigecycline, and monoclonal antibodies. C. difficile spores are highly resistant to killing by alcohol and most other disinfectants. In outbreaks of CDI, health care workers should be instructed to wash their hands with soap and water in addition to using alcohol-based hand disinfection when caring for infected patients. Patients should be isolated and contact precautions with gowns and gloves are recommended. Environmental cleaning with hypochlorite-based solutions is necessary to eliminate the spores.9 Antibiotic stewardship is also an important element in control strategies, with studies of antibiotic restriction showing benefit.15 In Australia, laboratory diagnosis of CDI is most commonly made through detection of C. difficile toxins A and B using enzyme immunoassay (EIA) kits. EIA kits have reported sensitivities of 75%–95%, but most of the evaluations reporting these sensitivities use faecal cytotoxin detection (a flawed test) as the gold standard.16 In addition, the positive predictive value of these tests declines markedly in situations where the prevalence of disease is low.16 Poor sensitivity of the assay is the likely explanation for the initial negative result of the enzyme-linked fluorescent assay in our case. Despite this limitation, EIA kits remain widely used because of their simplicity and relatively low cost. Commercial real-time PCR testing for toxin genes (usually tcdB), has better sensitivity (93%) and specificity (97%),16 and is now available in several Australian laboratories. Toxigenic culture — isolation of the organism followed by toxin testing of the isolate — is extremely sensitive, but it is labour intensive and takes at least 3 days.16 There is currently great debate about the value of an algorithmic approach to diagnosing CDI, whereby a sensitive screening test is used to screen out negatives, thus improving the positive predictive value of a secondary test, particularly when the prevalence of infection is low.17 Distinguishing C. difficile PCR ribotype 027 from other strains of C. difficile does not affect individual patient management, but is important for surveillance purposes. Some commercially available PCR methods can presumptively identify PCR ribotype 027 based on detection of binary toxin genes and the characteristic 18-base-pair deletion in the tcdC gene. An alternative, less expensive, approach is to screen for moxifloxacin resistance by using a 5 μg moxifloxacin disc on a lawn culture of C. difficile on Mueller-Hinton agar. Worldwide, most PCR ribotype 027 isolates are resistant to moxifloxacin,2 while, in Australia, the prevalence of resistance in all strains of C. difficile is 1%. (T V Riley, B Elliot and colleagues, unpublished data). Zones of inhibition for resistant strains (potentially PCR ribotype 027) are > 16 mm while for susceptible strains, they are ≥ 16 mm (T V Riley and colleagues, unpublished data). Isolates of moxifloxacin-resistant C. difficile identified in this way can then be sent for further typing. Given the arrival of C.difficile PCR ribotype 027 in this country, periodic PCR ribotyping of a representative sample of isolates now needs to be performed at designated reference laboratories Australia-wide, and recurrent funding is required for this task. This will be an important adjunct to local screening measures, and will also detect the emergence of virulent PCR ribotypes other than 027. An Australian Commission on Safety and Quality in Healthcare recommendation for hospital surveillance programs in all states and territories to monitor C. difficile was approved by Australian Health Ministers in November 2008. As yet, the states and territories have not implemented this recommendation, and there has been no collation or analysis of national surveillance data. With the identification of the first case of PCR ribotype 027 C. difficile infection acquired locally, it is important that clinicians in Australia are aware of the clinical picture, limitations of diagnostic tests, availability of further testing for PCR ribotype 027, new therapeutic approaches,18 and in-hospital control strategies for this infection.19 The solution to the bigger problem of the emergence of virulent strains of C. difficile continues to lie in the basics of surveillance, antimicrobial stewardship, infection control and environmental cleanliness. Ribotyping pattern of the Clostridium difficile strain isolated from the patient compared with a reference and an unrelated strain Patient isolate Unrelated strain PCR ribotype 027 reference strain 100-base-pair DNA ladder PCR = polymerase chain reaction.

Michael Richards MB BS, MD, FRACP · James Knox BSc(Med), MB BS, DTM · Briony Elliott BSc(Hons) · Kate Mackin BA/BSc(Hons) · Dena Lyras BSc(Hons), PhD · Lynette J Waring MB BS, FRCPA · Thomas V Riley PhD, FASM, FRCPath

To the Editor: Further to the recent article by Anstey and colleagues on community-acquired Klebsiella pneumoniae liver abscesses,1 we report two similar cases at our hospital in late 2010. Case 1: A 55-year-old Indonesian-born man was referred from general practice in October 2010 with a 5-day history of fever and progressive epigastric pain. He did not have diabetes, but did have dyslipidaemia. He had migrated from Indonesia in the 1980s; his most recent visit to Indonesia was in January 2010, for 3 weeks. As he had mildly deranged liver function test results, he was investigated with abdominal ultrasound and computed tomography (CT). Both showed a large multiseptate collection in the left lobe of the liver (Box, A). The liver collection was drained under radiological guidance, yielding a pure growth of K. pneumoniae. Urine culture was also positive for an identical isolate of K. pneumoniae. This man had a rapid clinical response to percutaneous drainage and was discharged on oral ciprofloxacin therapy. Case 2: A 25-year-old Indonesian-born man presented to our emergency department in early November 2010 after 2 days of headache, high fever and abdominal cramps, culminating in an acute confusional state. He had no significant medical or surgical history and had last visited Indonesia in March 2010, for 2 weeks. Initial therapy and investigations were aimed at excluding a diagnosis of meningitis. Results of a CT scan of the brain and of cerebrospinal fluid analysis were unremarkable. The patient remained acutely unwell and developed diarrhoea and right upper quadrant abdominal pain. Blood cultures were positive for K. pneumoniae within 48 hours of admission. Abdominal CT showed a large multiloculated abscess in the right lobe of the liver (Box, B). The liver abscess aspirate grew a pure culture of K. pneumoniae. The patient responded to treatment with ceftriaxone and large-volume percutaneous drainage. In both these cases, an antibiotic sensitive mucoid strain of K. pneumoniae was cultured. These cases add weight to the possibility raised by Anstey and colleagues that community-acquired K. pneumoniae liver abscess is indeed an emerging phenomenon in Australia. Further, the extended length of time between our patients’ travel to Indonesia and the clinical presentation (9 and 8 months, respectively) is suggestive of local (Australian) acquisition of the disease. Clinicians should consider abdominal imaging in cases of bacteraemia due to K. pneumoniae. Abdominal computed tomography scans showing Klebsiella pneumoniae liver abscesses

Kudzai N Kanhutu · Jeffrey J Post · Kate R Clezy · Hong Y L Foo

To the Editor: Interest in alternative therapies for Clostridium difficile infections (CDIs) is increasing as these infections become important causes of patient morbidity and mortality. Recurrent CDIs can be severe and difficult to treat. In-vitro data,1 followed by reports of the efficacy of tigecycline in the treatment of severe refractory cases of CDI,2 suggest that tigecycline should be considered as an alternative or adjunctive antimicrobial agent in these situations. To date, it has been used mostly as a “salvage” strategy in combination with other antibiotics in the face of clinical deterioration.2,3 We report the successful use of tigecycline monotherapy in the treatment of a patient with recurrent C. difficile colitis. An 83-year-old woman was admitted to hospital in July 2009 with acute diverticulitis. She was treated with intravenous cefotaxime (1 g three times daily for 6 days): her presenting fever and abdominal pain resolved but she developed watery diarrhoea. Despite positive stool cultures for toxigenic C. difficile, initial toxin testing by enzyme immunoassay (EIA [TechLab C. Difficile Tox A/B II]) of stool specimens was negative. After a 7-day course of oral metronidazole 200 mg three times daily, the diarrhoea abated. One month after discharge, our patient re-presented with anorexia, severe abdominal pain and diarrhoea. Six days of oral metronidazole, prescribed by her local doctor, had little effect. A computed tomography scan of the abdomen revealed diffuse thickening of the colon from the ileocaecal junction to the rectum, consistent with a pancolitis. Sigmoidoscopy showed grossly abnormal mucosa with pseudomembranes present. A diagnosis of C. difficile pseudomembranous colitis was made. After 10 days of oral vancomycin 250 mg, four times daily, her symptoms had resolved, and repeat sigmoidoscopy showed reversal of the mucosal changes. Six days later, the pseudomembranous colitis recurred. She rapidly responded to the recommencement of oral vancomycin, given as a tapering course over 6 weeks. Twelve days after completing the 6-week course of vancomycin, the patient presented with her third episode of colitis. Most reported strategies for recurrent CDI, such as faecal transplantation, probiotics or novel antimicrobials,4 were not practicable or available for timely use for our patient. Tigecycline, a broad-spectrum glycylcycline antibiotic, is available as part of the hospital formulary for the treatment of complicated skin and soft-tissue infections and complicated intra-abdominal infections. Encouraged by recent reports of success using tigecycline as adjunctive therapy for severe cases of CDI,2 we prescribed, as monotherapy, intravenous tigecycline 50 mg twice daily for 2 weeks. Our patient’s condition improved over 1 week. At 3-month follow-up, she remained asymptomatic, with repeat stool cultures and polymerase chain reaction (PCR) testing for C. difficile toxin negative at Days 75 and 107 following the last episode of colitis. Our case also highlights a diagnostic matter. In general, use of EIA to detect C. difficile toxin A or B is highly specific. However, in clinical settings where the prevalence of CDI is low, the positive predictive values for these assays are inadequate to rule in the diagnosis of CDI. Confirmatory laboratory testing using an alternative method (in this case, PCR) proved more reliable in the diagnosis of our patient’s recurrent CDI. Typing showed that our patient’s isolate was not PCR ribotype 027, a hypervirulent strain in Europe and North America associated with high mortality.5 We recommend consideration of tigecycline as a useful antimicrobial agent in the management of both recurrent and severe CDI.

Elaine Y L Cheong · Thomas Gottlieb

Objectives: To examine the experience of fear, the fear response, and factors affecting fear in adolescents undergoing school-based human papillomavirus (HPV) vaccination.Design, participants and setting: A purposive sampling strategy and qualitative methods, including observation and face-to-face interviews. Focus groups comprised adolescent girls who were involved in HPV vaccination in 2007 at schools in Sydney, New South Wales. Individual interviews were conducted with parents, teachers and vaccination nurses.Results: Data from observing vaccination days at three schools and from interviewing 130 adolescents in 20 focus groups, 38 parents, 10 teachers and seven nurses were included in the analysis. All participants discussed the issue of fear and distress experienced by adolescent girls in relation to HPV vaccination. Observations corroborated the focus group and interview data. Our results indicated that fear was promoted by witnessing the fear reactions of peers; perceived judgement by peers; lack of information or misinformation; and being vaccinated later in the day. Fear was moderated by procedural factors, the support of peers, appropriate knowledge, and nurses’ distraction techniques or approach. Fear also affected acceptance of HPV vaccination.Conclusions: Fear of HPV vaccination was a near universal experience among adolescents in the school setting and was often associated with significant distress that had an adverse impact on the vaccination process. School vaccination could be improved by proactively managing fear and distress.

Diana M Bernard MPH · Spring C Cooper Robbins PhD · Kirsten J McCaffery PhD · Caroline M Scott MHlthSc(Nurs) · S Rachel Skinner PhD, FRACP

Clinical record Two overseas backpackers presented to the emergency department of a tertiary referral hospital with epididymo-orchitis. Patient 1 was a 23-year-old unvaccinated Frenchman who presented in February 2009 with a 7-day history of unilateral, then bilateral, painful scrotal swelling. He had arrived in Australia a month before the onset of symptoms. He was treated with ceftriaxone and azithromycin for presumed sexually acquired epididymo-orchitis and was discharged “home” (to a youth hostel). He returned 10 days later with worsening scrotal pain, requiring admission for analgesia. Mumps serology revealed an elevated IgM but undetectable IgG titre. Test results for Chlamydia trachomatis and Neisseria gonorrhoeae polymerase chain reaction (PCR) on first-pass urine were negative. On reflection, the patient recalled mild parotid pain a week before his scrotal symptoms. He recovered after 2 days of inpatient treatment with non-steroidal anti-inflammatory drugs, paracetamol and bed rest. Patient 2 was a 25-year-old English traveller who presented to the same hospital in February 2009 with fever for 3 days, then unilateral scrotal swelling and moderately severe headache. He had arrived in Australia from England, via Thailand, a week earlier. He had been vaccinated against measles and rubella, but not mumps. On the sixth day of his illness, he required admission for pain management and inability to mobilise. Investigative ultrasounds showed features of epididymo-orchitis. An elevated mumps IgM titre was detected, and IgG was undetectable. Concurrently, a urinary PCR test for C. trachomatis was positive. He received oral doxycycline (for C. trachomatis), opiate analgesia and bed rest, and recovered after 4 days in hospital. Patient 3 was a 25-year-old unvaccinated French woman who presented to the same hospital in March 2009 with 2 days of fever, marked parotid swelling and dry mouth. She was a travelling companion of, and shared accommodation with, Patient 1. A saliva sample tested positive for mumps PCR. She was hospitalised for 3 days for pain management and cross-infection prevention. She was given non-opiate analgesia and oral rehydration. Droplet isolation precautions, such as isolation in a single room and use of facemasks, gloves and gowns by those attending her, were instigated. In this article, we use a series of cases to highlight the diagnostic challenges, risk factors and public health implications of mumps orchitis. Although mumps orchitis is well described in the literature, some general practitioners and hospital clinicians may be relatively inexperienced in its diagnosis and treatment because of the low prevalence of mumps in Australia. Mumps classically presents with a prodrome of fever, malaise and myalgia, and is followed by parotitis, which is usually bilateral.1 However, 10% to 20% of symptomatic cases of mumps have no parotid symptoms.2 The incubation period is 2 to 3 weeks, and the prodromal symptoms and parotitis usually persist for 7 days. People with mumps are infectious from 5 days before to 5 days after the onset of parotitis.3 Individuals without parotid symptoms are also infectious. Orchitis is the most common complication of mumps in post-pubertal males, occurring either unilaterally or bilaterally after 10 days of illness in up to 40% of this demographic with mumps.4 Less common complications include meningitis (in up to 10% of patients), encephalitis, pancreatitis, arthritis and oophoritis.2 Consequences of mumps orchitis include testicular atrophy (up to 50%), oligospermia or asthenospermia (up to 13%), and, rarely, sterility.2 There is conflicting evidence for the use of subcutaneous interferon alpha-2b in preventing testicular atrophy in mumps orchitis, and the drug is not given routinely.2 Two doses of the combined measles–mumps–rubella (MMR) vaccine confer detectable IgG antibodies in 95% of people.5 However, complete childhood vaccination is no guarantee of enduring immunity, as demonstrated by recent outbreaks in the United States and the Czech Republic where 84% to 90% of patients developing mumps had previously received two documented mumps vaccinations.6,7 Australian residents born between 1978 and 1982 are more susceptible to mumps, as they escaped natural mumps infection; were not targeted in the 1998 Measles Control Campaign, which involved MMR vaccination of primary school-aged children; and might have missed a second dose of MMR despite secondary school catch-up campaigns.8,9 Similarly, an under-vaccinated cohort (around 60% of eligible children) exists in the United Kingdom following anxiety created by a well publicised 1998 paper associating MMR vaccine with autism, which was later rebutted by several studies, reviews and conclusions reached by the World Health Organization’s Global Advisory Committee on Vaccine Safety.10 The three travellers described here missed childhood mumps vaccinations and opportunities for pre-travel vaccination. Herd immunity offers protection to unvaccinated individuals when more than 90% of the population is immune to mumps.10,11 Yet when susceptible people travel outside communities with high vaccination coverage, they lose the protection of herd immunity. Patient 2 probably acquired mumps in Thailand, and his case illustrates the infection risks for under-vaccinated adults travelling to mumps-endemic countries. In the absence of systemic symptoms, there are few clinical features that distinguish mumps from bacterial epididymo-orchitis. Sexually transmitted pathogens, including Chlamydia trachomatis and Neisseria gonorrhoeae, and other bacteria infecting the urinary tract, such as Escherichia coli, are common causes of epididymo-orchitis, and may be associated with urethral symptoms, or microscopic pyuria. The distinction between testicular swelling alone and epididymal involvement as a guide to bacterial causes is not helpful in practice because it is hard to assess clinically. Moreover, a recent review suggests that mumps itself can cause epididymitis in up to 85% of cases preceding a mumps orchitis.12 Other viral causes of orchitis include rubella, coxsackievirus, human parvovirus and echovirus. Lessons from practice Mumps transmission still occurs in Australia because of incomplete vaccination, either in Australia or overseas, or waning immunity over time. Mumps should be considered as a differential cause of epididymo-orchitis in an unvaccinated individual. For patients with epididymo-orchitis where no common urinary tract or sexually transmitted pathogen is isolated, mumps serological testing should be performed. There is no specific post-exposure treatment for contacts of a patient with mumps, but opportunistic vaccination of contacts could provide immunity against future exposure. Given ongoing mumps transmission in endemic regions, measles–mumps–rubella vaccination should be offered to Australians travelling abroad. Our report of Patient 2 highlights diagnostic uncertainty even with laboratory testing: results showed the presence of both C. trachomatis (positive urinary polymerase chain reaction [PCR]) and the mumps virus (positive IgM serology). Mumps IgM can be undetectable in vaccinated individuals (estimated 24%–51% sensitivity) but, when detected, it is highly specific (82%–96%).13,14 Clinical features of the patient’s condition, including orchitis and mild meningitis, were consistent with mumps, so concurrent infections were felt to be plausible. A convalescent serum sample showing a rising mumps IgG titre would have confirmed the mumps diagnosis, but testing was not possible because the patient resumed his travels. In severe cases requiring hospitalisation, or where there is diagnostic uncertainty and risk of transmission, serological investigations (or PCR assay before the emergence of detectable mumps IgM antibodies around the fifth day of the illness) are warranted to establish the diagnosis. Mumps is highly infectious and spread by droplets. Infected travellers pose a particular risk of transmitting mumps because use of shared accommodation and public transport places them in close proximity to others. Notification of mumps is required in Australia, and can help public health authorities identify outbreaks and manage infectious patients. Voluntary isolation outside hospital of young adults is encouraged by public health authorities; however, there are no routine practices for enforcing isolation for mumps (Dr Rosemary Lester, Deputy Chief Health Officer, Victoria, personal communication). As home isolation during the infectious period is impractical for travellers living in communal accommodation, hospital admission could be justified to protect the health of both the individual and the public. Moreover, there is no proven prophylaxis for contacts. Neither use of normal human immunoglobulin nor MMR vaccination has been shown to prevent acquisition after exposure to mumps.15 However, for contacts who have not had two documented MMR vaccinations, opportunistic offers of vaccination might, if taken up, confer immunity against future mumps exposure. In the demographic of young men, particularly when travelling, GPs and emergency physicians need to be aware of mumps as an alternative cause of epididymo-orchitis. As the case of Patient 1 shows, mumps transmission in Australia is ongoing. Clinicians treating epididymo-orchitis should ask the patient about parotitis symptoms. Where a typical bacterial pathogen is not found, mumps serological testing is recommended. If mumps is recognised, there is an opportunity to interrupt direct transmission by isolating patients, especially travellers living in close contact with potentially non-immune people. Finally, these case reports should remind clinicians to offer pre-travel MMR vaccination to young susceptible adults.

Joseph S Doyle MB BS, BA(Hons), MSc · Emma K Paige MB BS · Denis W Spelman MPH, FRACP, FRCPA

In the absence of conclusive evidence, the winner is the mask that has the confidence of clinicians Australian infection control strategies for pandemic influenza are influenced by world authorities — the Centers for Disease Control and Prevention (CDC) and the World Health Organization. WHO guidelines1 take into account the lack of health resources in many communities, and focus on affordability as well as reductions in infection risk. CDC guidelines2 presuppose a well resourced health sector and are aimed at achieving zero risk. The different approaches of the two organisations are manifest in their conflicting recommendations for the type of face mask to use in routine care of patients with influenza: CDC recommends the N95 respirator (equivalent to the P2 mask used in Australia), while WHO recommends the cheaper surgical mask. By giving the world free access to their guidelines, the organisations have saved countries the cost of guideline development. Yet, the gain in risk reduction with the adoption of the CDC’s recommendation is unknown and may not be cost-effective. Conversely, those who opt for the WHO guideline might not appreciate that health care workers (HCWs) in well resourced settings are unlikely to accept a strategy if they perceive it to be significantly riskier than the more costly alternative. The important question is whether either guideline is based on the best evidence and relates the potential risk reduction to the cost involved. A potted history of CDC’s change in preference from surgical to P2 masks may help those seeking well informed policies about the use of masks for routine patient care. The history of the use of masks by HCWs has been classified into three eras: development and testing (1905–1920); “awareness of the importance of masks” (1920–1940); and the “unimportance of masks secondary to antibiotics” (1940 and beyond).3 We nominate a fourth era, “over-importance of masks” (1990s to the present), which was set in motion by changes to CDC guidelines.4 The CDC’s decision to recommend P2 masks instead of surgical masks for routine care of patients with tuberculosis (TB) was prompted by an unusual outbreak of multidrug-resistant TB in HCWs.5 The CDC made the change despite acknowledging that (1) P2 masks were manufactured to filter industrial, non-pathogenic aerosols and tested to filter out 95% of 0.3 μm sodium chloride particles, not airborne or droplet-sized bioaerosols; (2) some surgical masks were also capable of filtering out 95% of 0.3 μm sodium chloride particles; and (3) the protective efficiency of P2 masks against specific pathogens was unknown. The revised recommendation instigated a widespread non-evidential assumption of a link between wearing masks and preventing aerosolised transmission of pathogens based on particle size: that is, it was assumed that P2 masks prevent disease transmission by airborne particles (≤ 5 μm in size), and surgical masks prevent transmission by droplet particles (> 5 μm in size).4 With neither laboratory nor in vivo efficiency data to compare mask types, why were P2 masks advocated to protect HCWs against TB? The answer lies in the principles of evidence-based medicine. Despite its deceptive moniker, evidence-based medicine values not only research evidence, but costs and the “needs and values” of stakeholders, including clinicians. CDC leaders moved from surgical masks to P2 masks to solve the “problem of merging scientific and theoretical data into a sound infection control approach for the protection of HCWs against tuberculosis”.6 The problem was not resolved on evidential grounds because the evidence was simply not there. Rather, the solution prioritised the needs and values of clinicians concerned that the surgical mask permits transmission of multidrug-resistant TB because it allows a gap between the face and mask. As a consequence, this revision bred a legacy that associates mask type with particle size rather than with HCWs’ needs and values.6 Confronted with a similar debate about influenza transmission, the Australian Department of Health and Ageing commissioned us to review the protectiveness of masks,7 antiviral prophylaxis and vaccination, and to develop evidence-based infection control algorithms8 for the protection of HCWs during a pandemic. Development of the algorithms was informed by the following considerations. Proper use of a mask is more protective than not using a mask, but research findings show that neither the P2 nor surgical mask type is statistically superior. This concurs with findings from a review9 as well as results of a randomised control trial showing non-inferiority of surgical masks.10 The effectiveness of antiviral prophylaxis against future strains cannot be tested. However, antiviral prophylaxis is effective against seasonal influenza when administered in the first 48 hours of illness and if the drug-resistance of the virus is low.11 Given the efficacy of seasonal vaccines, a novel pandemic vaccine may provide a similar level of protection. Implementing the recommendation that HCWs wear P2 masks for routine patient care in a pandemic has several difficulties, including cost and fit-testing. The need for fit-testing was added to both CDC and WHO infection control guidelines1,2 after occupational-acquisition of the severe acute respiratory syndrome (SARS) by HCWs. However, there is no evidence that fit-testing affords higher levels of protection than a comfortably fitting mask. During our study of stakeholders’ needs and values, local clinicians unanimously disputed the recommendation for the use of surgical masks for routine care despite the recommendation being only one part of our multi-tool infection control strategy, which included antiviral prophylaxis, vaccination and a face shield for eye protection.8 The clinicians told us that they were taught, when training in the management of SARS, that P2 masks give superior protection. Nearly a century ago, the recommendation for use of the gauze mask came with a warning that it should not provide the wearer with an “unwarranted feeling of security”, but should be considered as one part of an infection control process.12 Research evidence7 suggests that a surgical mask plus face shield, rather than a P2 mask, is sufficient protection against pandemic influenza, but will this measure serve as sufficient protection for a health care system that needs healthy HCWs to manage a pandemic-sized caseload? Conventional evidence-based principles give equal importance to research evidence, economic cost, and needs and values of stakeholders. When research is inconclusive, principles should be prioritised. WHO guidelines1 prioritise research evidence within the limitations of resources of different socioeconomic settings; CDC guidelines2 prioritise the needs and values of clinicians within the limitations of research evidence. The new infection control algorithms8 compensate for weak research evidence — they remove the “over-importance” given to masks by prioritising needs and values of HCWs, while presenting masks as just one component of an infection control strategy. Without seminal research evidence of influenza being transmitted exclusively by airborne transmission, and in the absence of studies testing for superior protection of P2 masks, it would be prudent for health care executives to view providing P2 masks to HCWs, not as an additional cost, but as an additional investment in the continuity of health service provision — and in the full knowledge that, on today’s evidence, P2 masks provide a level of protection equivalent to that of surgical masks.

Mary-Louise McLaws DipTropPubHlth, MPH, PhD · Jan Gralton BSc(Hons)

To the Editor: The article by Nelson and colleagues1 is a welcome contribution to understanding trends in varicella zoster virus (VZV) disease epidemiology in Australia, particularly ambulatory medical attendance, for which few data sources are available. They report a decline in general practitioner encounters for varicella (chicken pox) since the introduction of varicella vaccine that is consistent with the observed 69% reduction in national hospitalisation rates in children aged 1.5 to 4 years seen from January 2006 to June 2008, 2.5 years into the National Immunisation Program (NIP).2 Nelson et al also report a trend towards higher GP encounter rates for herpes zoster (HZ [shingles]) over time. Although it may be tempting to take this rise on face value, additional analyses are required for a full understanding of patterns in HZ-related health care use, particularly accounting for age and changes in the use of prescription medications, including antivirals and opioid analgesics. Increased HZ-related health care use commencing before varicella vaccine availability has been reported in countries with universal vaccination programs, including the United States3 and Australia,4 as well as in countries where varicella vaccination is not recommended universally, including the United Kingdom.5 In Australia, prescribing of antiviral drugs for HZ increased between 1995 and 1999.6 Australia’s ageing population will contribute to the increasing prevalence of HZ over time due to the propensity of the virus to reactivate with advancing age. An analysis that we conducted shows that an increase in crude national hospitalisation rates for HZ preceded varicella vaccine availability, and that there was no increase over time in age-specific and age-standardised rates (National Centre for Immunisation Research and Surveillance, unpublished data). In addition, the suggestion from modelling studies that HZ may increase under a universal varicella vaccination program because of reduced opportunity for immune boosting in adults has yet to be observed in the US, the country with the longest-standing universal program of varicella vaccination.3 These complexities in monitoring VZV-related diseases highlight the need for very sensitive and well validated surveillance systems for both varicella and HZ in Australia. Although the authors request consideration for a universal HZ vaccination program for those over 65 years, they may not have been aware that since April 2009 The Australian immunisation handbook, ninth edition, online version has had new guidelines on HZ vaccination recommending a single dose of live attenuated VZV vaccine from the age of 60 years.7 In March 2008, the Pharmaceutical Benefits Advisory Committee recommended that this vaccine was suitable for inclusion in the NIP for those aged 60 years, with a catch-up dose for all individuals aged 61 to < 80 years. A decision regarding NIP funding has not been made, possibly because of a shortage of vaccine due to manufacturing problems.

Anita E Heywood · Kristine K Macartney

Objective: To describe the use of surveillance and forecasting models to predict and track epidemics (and, potentially, pandemics) of influenza.Methods: We collected 5 years of historical data (2005–2009) on emergency department presentations and hospital admissions for influenza-like illnesses (International Classification of Diseases [ICD-10-AM] coding) from the Emergency Department Information System (EDIS) database of 27 Queensland public hospitals. The historical data were used to generate prediction and surveillance models, which were assessed across the 2009 southern hemisphere influenza season (June–September) for their potential usefulness in informing response policy. Three models are described: (i) surveillance monitoring of influenza presentations using adaptive cumulative sum (CUSUM) plan analysis to signal unusual activity; (ii) generating forecasts of expected numbers of presentations for influenza, based on historical data; and (iii) using Google search data as outbreak notification among a population.Results: All hospitals, apart from one, had more than the expected number of presentations for influenza starting in late 2008 and continuing into 2009. (i) The CUSUM plan signalled an unusual outbreak in December 2008, which continued in early 2009 before the winter influenza season commenced. (ii) Predictions based on historical data alone underestimated the actual influenza presentations, with 2009 differing significantly from previous years, but represent a baseline for normal ED influenza presentations. (iii) The correlation coefficients between internet search data for Queensland and statewide ED influenza presentations indicated an increase in correlation since 2006 when weekly influenza search data became available.Conclusion: This analysis highlights the value of health departments performing surveillance monitoring to forewarn of disease outbreaks. The best system among the three assessed was a combination of routine forecasting methods coupled with an adaptive CUSUM method.

Justin R Boyle BEng(Hons), PhD · Ross S Sparks MSc, PhD · Gerben B Keijzers MB BS, MSc(ClinEpi), FACEM · Julia L Crilly MN(Hons), PhD · James F Lind BS BM, BMedSci, FACEM · Louise M Ryan MA, PhD

Objective: To describe the epidemiology of adult patients hospitalised with influenza or pneumonia during a pandemic season in a sentinel network in Australia.Design, participants and setting: Prospective case series of adult hospital admissions to eight acute care general public hospitals (Influenza Complications Alert Network [Flu CAN] sentinel hospitals) in six Australian jurisdictions, 1 July to 4 December 2009.Main outcome measures: Demographic, clinical and outcome measures in patients admitted with laboratory-confirmed pandemic (H1N1) 2009 influenza in the sentinel hospitals compared with data from national notifications and intensive care unit (ICU) surveillance; admissions for influenza and pneumonia over time in each jurisdiction.Results: During 190 hospital-weeks of observation, there were 538 influenza admissions. Of these, 465 patients (86.4%) had the pandemic strain, representing 9.3% of total admissions with pandemic (H1N1) 2009 influenza (n = 4992) recorded nationally in 2009. Of these patients, 250/465 (53.8%) were women, 67/453 (14.8%) were Indigenous, and the median age was 46 years (interquartile range, 29–58 years). Comorbidities were present in 354/464 patients (76.3%), and 40 were pregnant (30.3% of women aged 15–49 years). FluCAN reported that 102 patients (21.9%) were admitted to ICUs, and of patients admitted to hospital, 26 (5.6%) died. FluCAN results were very similar to national notification data and published ICU admissions data. Of those who were followed to 30 days after discharge, 30 (6.5%) were readmitted. Of 1468 patients hospitalised with pneumonia, 718 (48.9%) were tested for influenza and 163 (11.1%) were co-infected with the pandemic strain.Conclusions: Sentinel surveillance systems can provide important and reliable information in a timely fashion and can monitor changes in severity of influenza during a pandemic season.

Paul M Kelly MB BS, PhD, FAFPHM · Tom Kotsimbos MD, FRACP · Anna Reynolds BSc, PhD · Richard Wood-Baker DM, FRACP · Bob Hancox MD, FRACP · Simon G A Brown MB BS, PhD, FACEM · Mark Holmes MB BS, MD, FRACP · Graham Simpson MD, FRCP, FRACP · Simon Bowler MB BS(Hons), FRACP · Grant Waterer PhD, FRACP, FCCP · Louis B Irving MB BS, FRACGP, FRACP · Christine Jenkins MD, FRACP · Phillip J Thompson MD, FRACP · Allen C Cheng FRACP, MPH, PhD

We present the first human case of anisakidosis acquired from eating locally caught fish in Australia. A 41-year-old woman experienced gastrointestinal pain, vomiting and diarrhoea of increasing severity over 3 weeks. All symptoms resolved spontaneously after a worm was passed in her faeces. Microscopic examination showed that it was a Contracaecum species larva of the family Anisakidae. Anisakidosis should be considered in patients with gastrointestinal symptoms who have recently eaten seafood. (MJA 2011; 194: 199-200) Clinical recordA 41-year-old Australian woman of Tongan descent presented to the Royal Adelaide Hospital with a 21-day history of intermittent, worsening gastrointestinal pain, vomiting and diarrhoea after eating raw, locally caught South Australian mackerel. She initially experienced vomiting, diarrhoea and right-sided abdominal pain. These symptoms resolved spontaneously after 2 days. Ten days later, she developed nausea, vomiting, right-sided abdominal cramps associated with a sore throat, rhinorrhoea, nasal congestion, cough with production of yellow sputum, myalgia, fevers, chills and sweats. She visited her local medical practitioner 2 days after these symptoms began, and was prescribed metoclopramide, which relieved the main symptoms. However, the symptoms returned 2 days later with increased severity. She was now vomiting up to six times a day and passing up to 10 bowel motions. She then presented to the emergency department and was given metoclopramide, hyoscine and intravenous fluids overnight. Her symptoms persisted and she was admitted to hospital the following day. On admission, the patient was alert, orientated and afebrile, and her blood pressure and heart rate were normal. Cyanosis and jaundice were not present. Her chest was clear, and her liver and spleen were not palpable. Her right lower quadrant was tender to deep palpation and she had a mild pharyngeal erythema. A complete blood examination, including eosinophil count and blood chemistry, was unremarkable. Three faecal samples were submitted to the Institute of Medical and Veterinary Science (IMVS), Infectious Diseases Laboratories, Adelaide; these were negative for macroscopic and microscopic blood, rotavirus, adenovirus, Clostridium difficile toxin and enteric bacterial pathogens, but mucus and inflammatory cells were present. Parasitology investigation was not requested. Three days after admission, the patient passed in a bowel motion a threadlike worm, about 2 cm long, which was still moving. This worm was forwarded to the IMVS for identification. All symptoms resolved on the day the worm was passed and the patient was subsequently discharged with no further follow-up required. The initial presumptive identification of the larva was an intestinal nematode, possibly a species of the Trichostrongylus or Ascaris genera. However, on further detailed microscopic examination, the larva was identified as a species of Contracaecum (Nematoda: Anisakidae) based on the presence of an intestinal caecum and ventricular appendix (Box) and the position of the excretory pore being at the base of the mouthparts. DiscussionAnisakidosis in humans is a well known disease resulting from accidental infestation with larvae of certain genera of anisakids, causing severe gastrointestinal disorders, allergic reaction and even death.1 This is the first reported case of anisakidosis in Australia. The allergic response can occur against live anisakids or food in which worms were killed by cooking or pasteurisation.2 The pathological changes that occur within the gastrointestinal tract during infestation with anisakids are the combined result of the direct action of the larva during tissue invasion and the complex interaction between the host immune system and the substances released by, or contained within, the parasite.2 In our case, the patient’s symptoms lasted about 3 weeks until a larva was passed in a bowel motion. Several cases of transient luminal anisakidosis have been reported in humans where a larva has been passed hours to weeks after consumption of infested seafood.3 In our case, early symptoms, including vomiting, diarrhoea and abdominal pain, could have been due to unsuccessful attempts of the parasite to penetrate the gastrointestinal wall. The medication prescribed before admission to hospital most likely relieved the symptoms for a limited time. We postulate that the larva survived and moved slowly down the gastrointestinal tract, causing additional symptoms. The sore throat, rhinorrhoea, nasal congestion and cough could have been a concurrent respiratory tract infection or a late hypersensitivity response. Other symptoms could have been due to dehydration as a result of vomiting and diarrhoea. Infestation with Contracaecum larvae has been reported less frequently than infestation with Anisakis larvae.4,5 In addition, reports of anisakid larvae in faeces are scarce.3 However, over 90% of cases described worldwide were caused by a single larva.2,3 The symptoms reported are diverse and cannot be related to specific morphotype of the parasite. For example, anisakidosis due to Pseudoterranova larvae is mostly benign in the United States, but can be a severe infestation in Japan.6 It is known that Anisakis type I larvae in Japanese mackerels caught on the eastern coast of Japan are less pathogenic than those caught on the western coast of the country.7 Of the many records of anisakidosis worldwide, only a few reports identified the larva to species level. This is due to the lack of species-specific morphological features in larval stages. Recently, molecular approaches have been developed to identify larvae specifically.8 In our case, it was not possible to identify the larva to a species level due to inappropriate preservation of the specimen. As human infestations occur after eating infested seafood, it is implied that the mackerel eaten by the patient was infested. In Australia, larval and adult stages of various species of anisakids infest a broad variety of fish, including mackerels.8-11 However, our case report represents the first human anisakidosis acquired from eating locally caught fish. Given that the popularity of consuming raw or undercooked fish (eg, sushi) is increasing, it is possible that anisakidosis is underdiagnosed in Australia due to the vague symptoms and limited diagnostic tests. For example, in a clinicopathological study of 92 cases of anisakidosis in Japan, over 60% of cases were diagnosed preoperatively as appendicitis, acute abdomen, gastric tumour or cancer, ileitis, cholecystitis, diverticulitis, tuberculous peritonitis, and cancer of the pancreas.12 An experienced parasitologist can visualise anisakid larvae with the naked eye in infested fish. However, the encysted larvae are rarely observed by the consumer, as the larval colouration and texture makes it difficult to differentiate larvae from the viscera or flesh of the seafood. The occurrence of larval anisakids, with zoonotic potential in Australian fish, raises the question as to the extent of undiagnosed cases of anisakidosis in Australia. We strongly recommend that a presumptive diagnosis of anisakidosis is considered by a treating practitioner in patients with gastrointestinal symptoms and a recent history of eating raw or poorly cooked seafood. Anterior end (A) and posterior end (B) of the Contracaecum larva recovered from the patient’s faeces Scale bars = 0.81 mm (A) and 0.32 mm (B). Diagnostic features include the thick body and annulated cuticle; intestinal caecum about 2.5 times longer than ventricular appendix; gonads not developed short; tail, with a single spine at the tip; body length and width 17.3 mm and 1.11 mm, respectively; nerve ring 0.33 mm from anterior end; oesophagus 2.93 mm long, 17% of body length; ventricular appendix 2.52 mm long, 86% of length of oesophagus; intestinal caecum 0.96 mm long, 33% of oesophageal length and 38% of length of ventricular appendix; anus 0.07 mm from posterior end and 0.4% of body length. Drawing by Shokoofeh Shamsi. This specimen has been deposited in the South Australian Museum, Helminthology collection.

Shokoofeh Shamsi BSc, MSc, PhD · Andrew R Butcher BSc, PhD

To the Editor: Resistant gram-negative bacteria (especially Escherichia coli) are a major and growing problem worldwide.1 Some strains are resistant to all available antibiotics.2 We report a patient with relapsing multi-resistant E. coli bacteraemia from a prostate infection. Relapses occurred despite treatment with numerous parenteral antibiotics that should have been effective. His infection was cured using azithromycin. A 69-year-old man developed dysuria and fever 2 days after a transrectal prostate biopsy; he had received ciprofloxacin for prophylaxis. He had travelled to Morocco 15 months before this episode and to Vietnam 1 year earlier. Blood and urine cultures grew E. coli that showed sensitivity to ceftriaxone, gentamicin and nitrofurantoin; intermediate sensitivity to ampicillin; and was resistant to ciprofloxacin, cotrimoxazole, tetracycline, doxycycline and cephazolin. He was treated with intravenous ceftriaxone for 2 weeks, followed by oral amoxycillin/clavulanate with a good clinical response. The patient relapsed 1 week after completion of this treatment, with dysuria and fever. E. coli was cultured from his urine, with the same sensitivities as before. He was treated for 4 days with ceftriaxone and 2 weeks with amoxycillin/clavulanate. One week after his second course of therapy, he re-presented with dysuria and fever. Urine and blood cultures grew E. coli with the same sensitivities as the previous cultures. A prostate ultrasound showed no focal abscesses. He received ceftriaxone 2 g and gentamicin 7 mg/kg, yet remained febrile. After 2 days, gentamicin was discontinued and azithromycin 500 mg orally daily was added. He became afebrile within 24 hours and his C-reactive protein level fell. Azithromycin was selected because its minimum inhibitory concentration was 4 μg/mL, and because of its efficacy against multiresistant salmonella.3 The patient was treated for 1 week with ceftriaxone and for 3 weeks with azithromycin. He remained asymptomatic and his C-reactive protein normalised. There were no further relapses. He underwent prostatectomy for confirmed prostate cancer 2 months after discontinuing azithromycin. There was no histological evidence of prostate infection. We believe that while travelling in Morocco or Vietnam, he acquired multiresistant E. coli, which was carried in his bowel and inoculated during transrectal prostate biopsy, a common infective risk of this procedure. We believe the initial treatment failure was due to poor antibiotic penetration of the acidic prostate environment, and azithromycin was responsible for the eventual cure. Case reports and clinical trials have shown successful use of azithromycin in treatment of chronic prostatitis due to Chlamydia trachomatis,4 and that azithromycin is active against E. coli.5 This case report demonstrates successful use of azithromycin for treatment of E. coli prostatitis resistant to ciprofloxacin.

Simon H T Jiang · Peter J Collignon

To the Editor: Although we welcome Boyd and colleagues’ recommendations for changes to infection control guidelines for Australian recipients of human growth hormone (hGH) and human pituitary gonadotrophin (hPG),1 we are concerned about the accuracy of the history provided and do not want it misrepresented. Boyd and colleagues refer to recipients living with anxiety since 1985, when the Australian Human Pituitary Hormone Program (AHPHP) was halted. However, Australian recipients were not aware of the risk until 1991–1992. After the first two recorded deaths from Creutzfeldt–Jakob disease (CJD) of women treated with hPG, their husbands fought for official recognition of the link between their deaths and the AHPHP. In 1992, media attention alerted recipients to the risk and initiated contact from treating doctors. Knowledge that this information had been withheld since 1985 angered recipients. Boyd et al’s article is contradictory in mentioning a possible single, discrete contamination event but also claiming that a higher-risk period is unknown. We challenge this — particularly on behalf of recipients who were informed they had received hormones from a batch identified as likely to have contained the transmissible agent that causes CJD. We dispute the stated lack of availability of detailed treatment information, as the Australian Government Department of Health and Ageing has meticulously obtained and archived patient notes of recipients from their treating doctors, which provide the most accurate source of data. Boyd and colleagues had access to records of the four women whose deaths resulted from AHPHP treatment. The records seem consistent with published data,2,3 confirming that the four women were treated between 1973 and 1978. This surely indicates a high-risk period and gives extra confidence to those treated outside this timeframe. Further, two of the three patients on whom autopsies were performed received treatment from an identical batch of hormones (44); one was treated with this batch only. The third patient received hormones from batches 43 and 45.2 Batch 44 was identified as contaminated, and it was theorised that tainted material was transferred to batch 45 via production equipment. The patient who did not undergo an autopsy received only batch 25, which was produced earlier and indicates another possible contamination event within the 1973–1978 period. Risk estimate percentages do not provide more confidence for recipients than is currently already growing. They do not bring back those who died, take away the guilt of the parents who consented to hGH therapy for their children, or change a history of suicides, broken marriages, anxiety, disgrace and despair. It is important that Boyd and colleagues do not blur the implications of their findings with the continued need for the Australian Government to maintain the Human Pituitary Hormone Trust Account, which was established to provide funding for counselling and support services for recipients, and ongoing support for this group of citizens whose lives changed forever and who continue to battle discrimination and delays when accessing health care. The recommendations inspire hope but provide no immediate relief. The passing of time brings confidence, but the record needs to respect the enormous impact on the lives affected.

Suzanne L Solvyns · David W Ralston

In reply: We thank Solvyns and Ralston for their thoughtful and heartfelt comments and their assistance in ensuring historical accuracy regarding the issues surrounding iatrogenic Creutzfeldt–Jakob disease (CJD) risk and recipients of the Australian Human Pituitary Hormone Program (AHPHP). Whether there is a need for ongoing support of AHPHP recipients for the foreseeable future was not considered in the scope of our report,1 but we unequivocally support provision of optimal health care services for them, which we believe relaxation of infection control measures will assist. The delays and manner in which many AHPHP recipients learned of their risk of CJD is certainly regrettable, but this was not the universal experience of recipients. Some were made aware of the risk by their treating practitioner in 1985,2 with their heightened personal anxiety commencing from that time. As stated in our report, we agree that the close temporal development of CJD in the four Australian human pituitary gonadotrophin recipients appears consistent with a single, significant contamination event,1 such as from tainting of a limited number of treatment batches — an observation broadly in keeping with the existence of a higher-risk treatment window. However, despite assertions to the contrary, data acquired from various sources by the Australian National Creutzfeldt–Jakob Disease Registry for analysis did not permit confident and consistent delineation of a higher-risk treatment group. This is not synonymous with saying that a higher-risk period was unknown to us.

Alison Boyd · Genevieve M J A Klug · Colin L Masters · Steven J Collins

To the Editor: Douglas and other senior epidemiologists have described the imminent demise of the Master of Applied Epidemiology (MAE) program.1 This program has produced around 160 graduates, at least 104 of whom (65%) are working in the broad area of infectious diseases epidemiology. It may be thought, therefore, that there is no further scope for employing MAE graduates. My experience indicates otherwise and I would be very surprised if it were unique. In a small epidemiology unit of a state reference laboratory, two of the six staff members are MAE graduates. One past employee, also an MAE graduate, is a close collaborator. Last year, on very short notice, this person was able to take over coordination of the infectious diseases epidemiology course in the Master of Public Health program (MPH) at the University of Melbourne after the previous coordinator, also an MAE graduate, accepted a position as Head of the School of Health and Social Development at Deakin University. The MAE graduates from the epidemiology unit contributed to the MPH teaching program as guest lecturers. The University of Melbourne was unable to attract a full-time infectious diseases epidemiologist to the coordinating position, suggesting a lack of suitably trained and experienced people in this discipline. There is no doubt that the MAE program produces suitably trained and experienced people, as attested by Douglas et al1 and Kelly et al in the Journal.2 It also fits with my experience as an employer of MAE graduates and a collaborator with other graduates and staff from the program. Continued funding of the MAE program was recommended by independent reviewers.3 There are many who believe that, not only should the MAE program continue, it should continue as part of a national infectious diseases prevention and control program.2 It is appropriate that similar Australian programs already exist for heart disease, cancer and diabetes. In a letter to the Journal, Givney eloquently described the arcane processes of interlocking acronym-rich, mandate-limited committees that constitute Australia’s approach to the national coordination of infectious diseases.4 This description would be recognised by many, who would agree with Givney and Kelly et al that the time has come for Australia to establish its own independent expert body for monitoring and control of infectious diseases.

Heath A Kelly

Objective: To determine antibody levels and estimate incidence of infection with pandemic (H1N1) 2009 influenza in children and pregnant women during the 2009 winter in Western Australia.Design, setting and participants: Two cross-sectional serosurveys using stored specimens collected for unrelated pathology testing, from before and after (3 August to 30 November 2009) circulation of the pandemic virus, and before commencement of the pandemic vaccination program. Specimens were from three groups: children aged 1–4 years, older children and teenagers aged 5–19 years, and pregnant women aged 21–45 years. The groups were geographically representative of the WA population.Main outcome measures: Reactivity against pandemic (H1N1) 2009 and seasonal A(H1N1) influenza viruses measured using haemagglutination inhibition (HI) assays.Results: Antibody titres were determined for 648 individuals in the prepandemic period and 736 in the postpandemic period. In the prepandemic period, HI titres ≥ 40 against the pandemic virus were found in 0 (95% CI, 0.0%–1.6%) children aged 1–4 years, 8.3% (95% CI, 5.3%–12.7%) of older children and teenagers, and 4.5% (95% CI, 2.4%–8.3%) of pregnant women. In postpandemic specimens collected from 1 September 2009 (when influenza activity had declined to near-baseline levels), estimated infection rates (subtracting prepandemic levels) were 25.4% (95% CI for difference, 18.6%–33.4%) in 1–4-year-old children, 39.4% (95% CI, 29.8%–48.5%) in older children and teenagers, and 10.2% (95% CI, 4.1%–17.1%) in pregnant women.Conclusions: A quarter of preschool children and about 40% of school-aged children and older teenagers had serological evidence of pandemic influenza infection during winter 2009, indicating high levels of mild or asymptomatic infection. The infection rate in pregnant women was much lower. The high infection rates in children help explain the reduced impact of the pandemic virus during the 2010 winter. Augmented by vaccination, there should be sufficiently high levels of immunity in the Australian population to significantly reduce the impact of the virus in future influenza seasons.

Gary K Dowse MB BS, MSc, FAFPHM · David W Smith BMedSc, MB BS, FRCPA · Heath Kelly MB BS, MPH · Ian Barr PhD · Karen L Laurie BSc(Hons), PhD · Anthony R Jones BSc, MASM · Anthony D Keil MB BS, FRCPA · Paul Effler MD, FAFPHM

To the Editor: Point prevalence studies have been used for many years as markers of antimicrobial consumption,1,2 but they have suffered from a lack of standardisation with regard to the populations studied and the data collected. These deficiencies make it difficult to generalise the data outside the study populations. In recent years, the European Surveillance of Antimicrobial Consumption (ESAC) has sought to overcome these weaknesses by implementing a web-based point prevalence survey in 20 European countries using standardised definitions for site of infection, indication and quality indicators, such as whether the indication for prescription is documented in the case notes.3 As Australian studies of this type have not been published, we undertook a pilot study to assess whether this point prevalence tool is feasible and useful in an Australian setting. All surgical inpatients (excluding intensive care patients) in Sydney’s Royal North Shore Hospital (a 541-bed tertiary referral hospital) at 8 am on a single day in December 2009 were included. Current prescriptions for antimicrobials were captured from the medication prescription charts, and data on duration of therapy, dose and route of administration were collected for that point in time to give a “snapshot” of prescribing on that day. We reviewed patients’ medical records to establish site of infection, indication for treatment, and whether the reason for the antimicrobial was documented. ESAC codes for site of infection and indication were used. Of 178 patients, 95 (53%) had been prescribed 140 antimicrobials (ESAC mean, 30% of patients; range, 19%–59%).3 Cephazolin was the most commonly prescribed antimicrobial (32/140; 23%), and 115 antimicrobials (82%) were administered intravenously. Intra-abdominal sepsis (31/140; 22%) and cellulitis or wound infection (21/140; 15%) were the most common anatomical sites requiring treatment. Of the 140 prescriptions, 48 (34%) were for community-acquired infections, 29 (21%) were for postoperative infections, and 35 (25%) were for surgical prophylaxis. Of the 35 prescriptions for surgical prophylaxis, 14 (40%) were administered for more than 1 day (ESAC, 57%).3 The reason for initiation of the antimicrobial was documented in the patient’s medical notes for 95 of 140 prescriptions (68%) (ESAC, 64%).3 Use of the ESAC methodology allowed us to benchmark our results against published international reports. However, it gave no information on the appropriateness of the prescriptions or whether they adhered to antimicrobial guidelines. The ESAC point prevalence tool is easily applicable to the Australian health care system and provides useful information on antimicrobial consumption and quality indicators at an institutional level. Addition of questions regarding appropriateness of prescribing could be incorporated to give further relevant information.4 Use of the same methodology in other Australian centres would enable comparison across institutions and, potentially, national and international collaboration.

Jennifer A Kieran · Rosaleen G O’Doherty · Bernard J Hudson

Objective: To assess background pre-pandemic cross-reacting antibodies to the pandemic (H1N1) 2009 virus in older populations in Australia.Design, setting and participants: Data were opportunistically generated from three cross-sectional pre-pandemic studies involving people aged 60 years or older: a 3-year (2006–2008) study of influenza outbreaks in aged care facilities (ACFs) in Sydney; an investigation of a respiratory virus outbreak in an ACF in rural New South Wales in June 2009; and a non-influenza serosurvey undertaken in NSW in 2007 and 2008.Main outcome measure: Prevalence of pandemic (H1N1) 2009 haemagglutination inhibition (HAI) antibody titres ≥ 1:40 (putative protective level) in pre-pandemic sera.Results: In total, 259 serum samples from individuals aged 60 years or older (range, 60–101 years) were tested. More than half of the individuals tested were women (151/259; 58.3%). About a third of individuals (37.5%) had cross-reacting HAI antibody titres ≥ 1:40. The prevalence of cross-reacting antibodies was highest in the oldest age groups (≥ 85 years), with more than 60% of these people having HAI antibody titres ≥ 1:40. The proportion of subjects with HAI antibody titres ≥ 1:40 decreased significantly and successively in younger groups to only 12% of those aged 60–64 years.Conclusions: Our study suggests a pre-existing influenza A antibody reserve in most of the oldest group of people that was cross-reactive to the new pandemic (H1N1) 2009 virus; this is likely to be lifelong and to have provided them with clinical protection against the first wave of the pandemic. Pandemic influenza control measures need to focus more on younger adults naive to the pandemic virus and at increased risk of severe disease.

Robert Booy MD, FRACP, FRCPCH · Gulam Khandaker MB BS, MPH, DCH · Leon G Heron MB ChB, FRCPA, FAFPHM · Jiehui Yin MB BS, MPH(Hons) · Bridget Doyle BAppSci, GradDipEd · Katherine K Tudo BMedSci · Linda Hueston BSc, MSc · Gwendolyn L Gilbert MD, FRACP, FRCPA · C Raina MacIntyre MB BS(Hons), PhD, FRACP · Dominic E Dwyer MD, FRACP, FRCPA

Human infection with Rickettsia felis has been reported in most parts of the world, and R. felis has recently been confirmed in cat fleas in Western Australia. The clinical presentations of R. typhi and R. felis are similar, and in the past, the incidence of R. felis infection may have been underestimated. We describe the first reported cases of probable human R. felis infection in Australia. Two adults and three children in Victoria contracted a rickettsial disease after exposure to fleas from kittens. Molecular testing of fleas demonstrated the presence of R. felis but not R. typhi. Clinical recordsPatient B, a previously well 9-year-old girl, was admitted to a children’s hospital in Melbourne, Victoria, in April 2009 with severe abdominal pain, fevers to 39°C and a non-pruritic erythematous macular rash, initially present on the trunk and then spreading to the upper limbs and face (Box 1). The patient described a prodrome of 5 days of fever and malaise, with occasional vomiting and diarrhoea. She had been appropriately vaccinated, had no drug allergies, and did not regularly take any medication. On initial examination, the girl appeared unwell, with pitting oedema of the ankles and a generalised macular rash. There was no hepatosplenomegaly or significant lymphadenopathy. Initial laboratory test results indicated leukopenia (white blood cell count, 3.0 × 109/L [reference range (RR), 4.5–13.5 × 109/L]), lymphopenia (lymphocytes, 0.42 × 109/L [RR, 1.5–6.5 × 109/L]), thrombocytopenia (platelet count, 38 × 109/L [RR, 150–400 × 109/L]), hyponatraemia (Na+, 133 mmol/L [RR, 135–145 mmol/L]), hypoalbuminaemia (serum albumin, 19 g/L [RR, 33–47 g/L]), and elevated transaminase levels (aspartate aminotransferase, 168 IU/L [RR, < 55 IU/L]; alanine aminotransferase, 177 IU/L [RR, < 55 IU/L]). Treatment with ticarcillin–clavulanic acid and gentamicin was commenced. Urine and blood cultures were ordered, as well as serological tests for a range of infectious diseases. The patient lived with her parents and two siblings in suburban Melbourne on a hobby farm next to a wooded reserve notable for stagnant water and mosquitoes. The family had many pets, including a dog, goat, ducks, budgerigars, mice and a domesticated rat. They had never travelled outside Australia, and had not recently had visitors from overseas. About 3 weeks before the onset of the illness, the family had acquired a pair of kittens (Cat 1 and Cat 2) from a farm in Lara, a rural suburb in Victoria, and had given Cat 2 to a neighbour. Patient B had ongoing persistent fever and severe abdominal pain. Her platelet count remained low, and her hepatic function, coagulopathy, hyponatraemia and hypoalbuminaemia worsened. On Day 3 of her admission, she developed pulmonary oedema and required a short stay in the intensive care unit, during which she received azithromycin, albumin and frusemide, as well as intensive supportive therapy and monitoring. She was given intravenous immunoglobulin (IVIG) 2 g/kg for possible Kawasaki disease but showed no response. Also on Day 3 of Patient B’s hospitalisation, her 8-year-old sister (Patient C) presented with fevers to 40°C, mild abdominal pain and a rash on her torso. On examination, she appeared to be well, but had florid facial flushing, a macular rash spreading to the limbs, tender cervical lymph nodes and a mildly tender abdomen. Patient C’s initial laboratory test results indicated mild leukopenia (white blood cell count, 4.5 × 109/L) and hyponatraemia (Na+, 132 mmol/L). Treatment with ticarcillin–clavulanic acid and gentamicin was commenced. Over 48 hours she became thrombocytopenic (platelet count, 77 × 109/L), with worsening abdominal pain and hyponatraemia (Na+, 132 mmol/L), and elevated alanine aminotransferase (75 IU/L). She was given IVIG 2 g/kg for possible Kawasaki disease. Her condition improved rapidly. On Day 7 of Patient B’s hospitalisation, Patient D, the girls’ 4-year-old brother, presented with a fever of 39.6°C and five erythematous macules on his legs and trunk. He was otherwise well. Laboratory test results for Patient D showed leukopenia (white blood cell count, 4.0 × 109/L), with no other abnormalities. He was admitted for observation without treatment. The three siblings were discharged home on Day 11 of Patient B’s hospitalisation, without definitive diagnoses. Patients C and D had episodes of fever for 1 week, but remained well otherwise. A phone review on Day 18 found that the three children were well and afebrile. However, their maternal grandmother (Patient E) had had 3 days of fever and rigors and had been admitted to another hospital for observation. On advice from the children’s doctor, Patient E’s treating doctor administered doxycyline and her condition subsequently improved. It was also discovered that the neighbour who had been given Cat 2 (Patient A) had become unwell 2 days before Patient B, with a non-specific febrile illness that had settled by the time Patient B was admitted to hospital. She was therefore the initial case in the cluster. All patients had had extensive close contact with one or both of the cats. The children’s parents had minimal contact with the cats and were asymptomatic. The family reported that both cats had flea (Ctenocephalides felis) infestations when they acquired them. Cat 1 no longer had fleas after having been treated topically with insecticide, but its serum was tested for typhus-group rickettsial species. Because it was unwell, Cat 2 had been euthanased before blood samples could be taken. As collecting fleas from the two kittens was not possible, fleas from other cats of the group into which they were born, including the kittens’ mother, were collected for molecular analysis to identify any rickettsial species they carried. Serological testing was performed using indirect microimmunofluorescence assay (IFA).1,2 Initial serological analysis (in April 2009) for the presence of both spotted-fever-group and typhus-group rickettsial antibodies was undertaken on Patients B and C. The results showed the presence of typhus-group but not spotted-fever-group rickettsial antibodies. A month later (May 2009), serological testing was repeated for Patients B and C, and initial testing was done for Patients D, E and A. The tests showed rising typhus-group rickettsial antibody titres in patients B, C and E and high titres in patients A and D. In addition, Patient C showed clear evidence of seroconversion (Box 2), while both parents were negative for rickettsial antibodies. Serological testing undertaken on Cat 1 also showed the presence of typhus-group rickettsial antibodies (Box 2). DNA was extracted from the serum of Patient C (buffy coat [white cell layer] was not available), and Cat 1, and from pooled and crushed cat fleas that were collected from cats in the group that Cat 1 and Cat 2 had come from. A rickettsial real-time polymerase chain reaction (PCR) test was performed on the extracted DNA samples.3 The fleas, but not the patient’s or cat’s serum, were positive for rickettsial DNA. A 1077 base-pair fragment of the rickettsial citrate synthase gene was amplified and sequenced.4 This sequence was compared with the validated rickettsial species5 and showed closest phylogenetic similarity to Rickettsia felis, with a sequence similarity of 99.7% (1074/1077 base pairs). Rickettsia typhi DNA was not detected in the cat fleas. The citrate synthase gene (gltA) sequence analysis using the neighbour-joining algorithm is shown in Box 3. DiscussionThe five patients described here are the first reported cases of probable human R. felis infection in Australia, and the analyses provide the first molecular evidence of R. felis in cat fleas in Victoria. It has been previously detected in cat and dog fleas in Western Australia by molecular analysis.6 Human infection with R. felis has been reported in most other parts of the world.7-10 While genetically a member of the spotted-fever rickettsia group, R. felis behaves clinically and serologically like a typhus-group rickettsia and is transmitted by fleas. Antibodies induced by R. felis react with typhus-group rickettsiae in serological tests, rather than with spotted-fever-group rickettsiae. A petechial rash is an infrequent sign of infection, and a macular or maculopapular rash is present in only 50% of patients (Box 1). The high attack rate and severity of infection noted in this cluster may be due to the heavy flea infestation that was reported. Resolution without therapy is well described in rickettsial infection. Only two patients (B and C) received antimicrobial therapy with known activity against rickettsial species. The five patients showed a strong positive result for the presence of typhus-group antibodies. Patient C’s clear seroconversion was consistent with recent acute R. felis or R. typhi infection.7 While exposure to either R. felis or R. typhi could have led to Cat 1 producing typhus-group antibodies, only R. felis DNA was detected in the cat fleas. It is common for blood from cats infected with R. felis to be negative for rickettsial DNA,8 as in this case. Cat 1 still had antibodies to R. felis but either had cleared the infection, or the organism was present in tissues other than peripheral blood. In a previous experimental exposure of cats to R. felis-positive fleas, 13 of 16 cats were positive by serological testing using IFA, but only five of the 16 were positive by PCR.11 The human cases reported in this study were only identified serologically, and as the clinical presentations of R. typhi and R. felis are similar, R. typhi cannot be completely ruled out as the causative agent. However, given the molecular data from the cat fleas, R. felis is the more likely causative agent. In the past, the incidence of R. felis infection in patients with raised typhus group antibody levels may have been underestimated, with the causative agent probably reported as R. typhi when it may have been R. felis — a confusion that has been seen in other studies.8,9 1 Widespread erythematous macular rash, Patient B 2 Serology results of five seropositive patients and a cat exposed to rickettsial infection, 2009 Patient/ cat Sex, age in years Day of onset* Status in family Rickettsia group Serum antibody titre April May June A F, 63 − 2 Neighbour SFG nd < 1/128 nd TG nd 1/16 384 nd B F, 9 1 Child SFG 1/128 1/128 nd TG 1/1024 1/8192 nd C F, 8 3 Child SFG 1/128 1/256 nd TG < 1/128 1/16 384 nd D M, 4 7 Child SFG nd 1/128 nd TG nd 1/16 384 nd E F, 59 15 Grandmother SFG nd < 1/128 < 1/128 TG nd 1/1024 1/2048 Cat 1 F, < 1 na Pet SFG nd nd < 1/128 TG nd nd 1/512 na = not applicable. nd = not done. SFG = spotted-fever group (ie, Rickettsia australis and R. honei). TG = typhus group (ie, R. prowazekii and R. typhi). * Compared with Patient B’s admission (Day 1). 3 Condensed phylogenetic tree comparing the DNA fragment sequenced in this analysis (“Rickettsia felis [Lara]”) with validated rickettsial species Relationship of a 1077 base-pair fragment of the gltA gene of Rickettsia felis (Lara) among other validated rickettsial species, with the core spotted-fever-group rickettsiae truncated. The tree was prepared using the neighbour-joining algorithm.* Bootstrap values are indicated at each node. The scale bar represents a 2% nucleotide divergence. * Molecular Evolutionary Genetics Analysis (MEGA) software, version 4.0, 2007 [free internet download].

Molly Williams MB BS · Leonard Izzard BSc, PhD · Stephen R Graves MB BS, PhD, FRCPA · John Stenos BSc, PhD · Julian J Kelly MB BS, FRACP

To the Editor: We share the concern of Fernando and colleagues about the recent emergence of multidrug-resistant bacteria via travellers returning to Australia and the resulting reduction of therapeutic options for such patients, who may have entered a “post-antibiotic era”.1 In countries such as India that lack an integrated laboratory network, the precise magnitude of the threat of plasmids encoding blaNDM1 type metallo-β-lactamases is unknown. Molecular testing for the NDM-1 type of β-lactamases might be available at only two or three national laboratories, and most hospitals will have no such testing facilities. During replication of multidrug-resistant bacteria carrying blaNDM1 type metallo-β-lactamases, susceptibility to some older antimicrobial agents might be retained. This was evident in two multidrug-resistant Enterobacteriaceae isolates that were identified at the Sant Parmanand Hospital (a 140-bed tertiary-care, multidisciplinary hospital that serves the population of Delhi and two adjoining townships), at which blaNDM1 metallo-β-lactamase testing is not available. From March to August 2009, 509 Enterobacteriaceae isolates were identified — Klebsiella pneumoniae (368), Escherichia coli (112), Salmonella enterica serotypes Typhi, Paratyphi A, and Paratyphi B (20) and Proteus species (nine). Bacteria were identified by morphological, biochemical and serological characteristics. Antimicrobial susceptibility was tested by the disk diffusion method, according to the United States Clinical and Laboratory Standards Institute guidelines. Two of the K. pneumoniae isolates were resistant to meropenem, piperacillin–tazobactam, cefepime, amoxicillin–clavulanic acid, amikacin, gentamicin, ciprofloxacin and tigecycline. One had been isolated from the pulmonary secretions of a 45-year-old woman in March 2009; it was susceptible to ofloxacin and chloramphenicol. The other had been isolated from the urine of a 55-year-old woman in July 2009; it was susceptible to chloramphenicol and nitrofurantoin. Among all the K. pneumoniae isolates, there were 53 resistant to meropenem, 113 resistant to ceftriaxone, 82 resistant to gentamicin and 111 resistant to ciprofloxacin. Among all the E. coli isolates, there were three resistant to meropenem, 38 resistant to ceftriaxone, nine resistant to gentamicin and 35 resistant to ciprofloxacin. The proportion of meropenem- and gentamicin-resistant isolates was significantly higher for K. pneumoniae compared with E. coli (Fisher exact test, P < 0.001). Older antimicrobial agents such as ofloxacin, chloramphenicol and nitrofurantoin, developed in the 1940s and 1950s, would not be the initial choice for today’s clinicians managing patients with severe multidrug-resistant infections. However, they should be considered before declaring that the post-antibiotic era has arrived.

Subhash C Arya · Nirmala Agarwal

Names are more than just labels used to identify diseases. They can be windows into the discovery, characteristics and attributes of the disease. Toponymous diseases are diseases that are named after places. Hendra, Ross River, Bairnsdale, Murray Valley and Barmah Forest are all examples of Australian places that have had diseases named after them. They all have unique and interesting stories that provide a glimpse into their discovery, history and culture. Because of perceived negative connotations, the association of diseases with placenames has sometimes generated controversy.

Ranil D Appuhamy BSc, MB ChB, MIPH · Jan Tent BA(Hons), DipEd, PhD · John S Mackenzie PhD, FASM, FACTM

HIV will only be defeated when behavioural means of prevention become the basis of the global response For nearly three decades, the world has struggled to manage the vast human, social, economic and political impact of the emergence of HIV/AIDS. The history of the global HIV/AIDS pandemic is broadly divisible into two phases — before and after the introduction, in 1996, of effective antiretroviral therapy (ART). The first phase of the pandemic — from the earliest reported cases of HIV/AIDS in New York in October 1982 until treatments became available in 1996 — constituted nothing less than a public-health catastrophe. In many countries, notably the United States and South Africa, political leaders responded to the appearance of HIV/AIDS with a toxic combination of ignorance, prejudice and political cynicism directed at those in whom the disease had first appeared in industrialised countries — gay men, sex workers and injecting drug users. Only a few countries, including Australia, moved decisively during the 1980s to control HIV/AIDS and to prevent its spread into the general community. These pragmatic prevention strategies were based on rapidly accumulating evidence that simple changes in sexual and needle-sharing behaviour among young people, complemented by access to condoms and clean needles, dramatically reduced HIV transmission rates. By the mid to late 1990s, there was clear evidence from published studies that such strategies were effective in containing new HIV infection rates,1,2 and their success in Australia and a small number of other countries was undeniable. Yet almost none of these strategies were implemented on a sufficiently large scale or in time to reduce the impact of HIV/AIDS in regions and countries then largely unaffected by the problem. To put it mildly, an epic failure of leadership and political will to accept and act on scientific evidence turned a potentially containable problem into a pandemic that, by the late 1990s, was beyond control. Nature created HIV, but anti-prevention politicians and their associates created the HIV pandemic.3 The human consequences of the HIV pandemic, and the failure to contain the problem in the mid 1980s, are shocking. Since 1982, HIV has infected 60 million people, and there have been 25 million deaths from AIDS caused by HIV infection.4 The second, and much more encouraging and enlightened, phase of the HIV pandemic dates from 1996, with the development and introduction of highly effective ART. In almost all industrialised countries, access to this lifesaving treatment quickly became virtually universal. From the late 1990s, deaths from AIDS declined and HIV became a more manageable chronic condition. This in turn led to an abatement of the worst excesses of fear-mongering and a perceptible decline in HIV-related stigma and discrimination. The international response to HIV/AIDS was galvanised by two highly significant developments. Firstly, in 1996, the United Nations (UN) established UNAIDS, a specialised UN agency set up to provide strategic direction and to develop and oversee a coordinated international response to HIV/AIDS. Secondly, in 2002, the G8 countries (United Kingdom, US, France, Germany, Italy, Japan, Canada and Russia) established the Global Fund to Fight AIDS, Tuberculosis and Malaria. The Global Fund was charged with funding and supporting the large-scale distribution of ART in developing countries, especially African countries, which have been most grievously affected by the uncontrolled spread of HIV/AIDS. These two institutions — one handling strategy and politics and the other raising and disbursing money — have brought about tremendous improvement in the international management of HIV/AIDS. Since 2002, the Global Fund has sourced nearly US$20 billion from public and private donors,5 of which about US$10 billion has been applied to the subsidised distribution of HIV/AIDS treatment, care and prevention services in some 140 poor and developing countries. The Global Fund is now the major international financer of programs to eradicate mother-to-child transmission of HIV and to support harm reduction among injecting drug users. At the end of December 2009, programs financed directly by the Global Fund were providing ART to 2.5 million people.6 Together with ART distribution financed by the US under the President’s Emergency Plan for AIDS Relief, more than four million people in low- and middle-income countries now have access to ART, representing about 40% of those in urgent need. Sensible HIV strategies backed with large funding have begun to stabilise the spread of HIV/AIDS in most high-burden African countries. In Ethiopia’s capital, Addis Ababa, for example, the rollout of ART has led to a decline of about 50% in adult AIDS deaths over a period of 5 years.6 As the number of global deaths from AIDS has fallen, the number of those living with HIV has increased. There are now some 33.4 million people living with HIV infection.4 But, despite these advances, each year about 2.7 million people acquire HIV and about two million people die from AIDS, mostly within the developing world.4 Other regions have not responded as well as Africa. * Eastern Europe and Central Asia is one of the 10 regions defined and used by UNAIDS. The region includes Armenia, Azerbaijan, Belarus, Bosnia and Herzegovina, Bulgaria, Croatia, Estonia, Georgia, Kazakhstan, Kyrgyzstan, Latvia, Lithuania, the Republic of Moldova, Romania, the Russian Federation, Tajikistan, Turkmenistan, Ukraine and Uzbekistan. In Eastern Europe and Central Asia,* many national governments reject the lessons of how the spread of HIV can be contained through education and behavioural change. They oppose the widespread availability of condoms and the introduction of needle and syringe programs for those at highest risk of HIV infection. Consequently, rates of HIV infection in these countries are increasing at an alarming rate. In Eastern Europe and Central Asia, an estimated 110 000 people were newly infected with HIV in 2008, bringing the number of people living with HIV in the region to 1.5 million, compared with 900 000 in 2001 — a 67% increase over this period.7 Ukraine and the Russian Federation are experiencing especially severe and growing national epidemics. With an HIV prevalence of over 1.6% in adults, Ukraine has the highest infection level reported in all of Europe.4 So, as we mark the recent occasion of World AIDS Day 2010, the best that can be said about the state of the global fight against HIV/AIDS is that our successes have been relative. The world supported care and treatment for people with HIV/AIDS when effective therapies became available. During the boom conditions of the 1990s, it was relatively easy for the largest donors to put real financial resources behind the distribution of ART that saved millions of lives in the poorest countries. But economic times have changed. In October 2010, the Global Fund went to donors seeking some US$20 billion for the period 2011–13 so that the most urgent unmet need for ART in the developing world could be met.8 But, instead of US$20 billion, donors provided only US$11.7 billion. (Australia was one of the few countries that increased its support for the Global Fund.) In summary, the first phase of the HIV/AIDS pandemic was chaotic and lamentable. The second phase was encouraging and hopeful. We are now entering the third phase of the response. At a critical moment, transient economic difficulties in the donor countries threaten to jeopardise the great progress that has been made since the late 1990s. It would be appallingly callous and retrograde to take HIV treatments away from those whose lives have been saved thanks to the efforts of donors working through the Global Fund. We must not falter in our determination to provide universal access to care and treatment to all who still require it. The costs of ensuring universal access to ART by 2015 are, in the scheme of things, trivial compared with overall global development assistance budgets, not to mention expenditure on armaments and weapons, while the benefits are abundantly obvious. The third phase of the global response to HIV/AIDS must be dominated by a renewed commitment to behavioural prevention as the surest and most sustainable way to contain the pandemic. We can contain HIV by improving access to treatments and providing care to people with the disease. But HIV will only be defeated and eradicated when the lessons of behavioural prevention that we developed and applied in Australia two decades ago become the basis of the global response.

William D Bowtell BA(Hons)

Objective: To describe recent trends among men who have sex with men (MSM) in age at diagnosis of HIV in Victoria.Design and setting: Analysis of Victorian HIV surveillance data from (i) passive surveillance (2000–2009) and (ii) the Victorian Primary Care Network for Sentinel Surveillance (VPCNSS) (2006–2009). Age-trend comparisons were made using syphilis and gonorrhoea enhanced surveillance.Main outcome measures: HIV diagnoses, HIV testing and behavioural indicators by year and age group among MSM.Results: Following a period of sustained increase between 2000 and 2007, the median age at HIV diagnosis among MSM declined significantly, from 38.8 years in 2007 to 35.3 years in 2008 (P = 0.023), remaining at 35.9 years in 2009. Between 2007 and 2008, the median age of syphilis and gonorrhoea notifications also declined, from 40.6 to 36.0 years and from 32.3 to 29.3 years, respectively. The median age of HIV testing among MSM in the VPCNSS population remained constant between 2006 and 2009, at 33.0 years. Compared with older MSM, those aged less than 35 years were more likely to have never previously been tested for HIV (relative risk [RR], 1.36 [95% CI, 1.30–1.41]); to not know the HIV status of their regular partner (RR, 1.11 [95% CI, 1.01–1.21]); and to report inconsistent condom use with casual partners (RR, 1.07 [95% CI, 1.01–1.14]) and regular partners (RR, 1.07 [95% CI, 1.00–1.14]).Conclusions: Younger MSM in Victoria may be at increasing risk of HIV infection. Enhanced methods of monitoring HIV and sexually transmitted infection transmission in younger MSM are needed, as well as prevention messages to target this group, who may not fully understand their HIV risk.

Carol El-Hayek BSc, MEpi · Isabel Bergeri PharmD, MScEpi · Margaret E Hellard FAFPHM, FRACP, PhD · Alisa E Pedrana BBiomedSc(Hons) · Nasra Higgins MEpi · Alan Breschkin PhD · Mark Stoové PhD