Infectious diseases

Incorrect order of authors: In “ASID (HICSIG) position statement: infection control guidelines for patients with influenza-like illnesses, including pandemic (H1N1) influenza 2009, in Australian health care facilities” published online on 21 September 2009 and in the 19 October 2009 issue of the Journal (Med J Aust 2009; 191: 454-458), John K Ferguson was incorrectly listed as the first author of the article. The correct order of authors is: Rhonda L Stuart, Allen C Cheng, Caroline L Marshall and John K Ferguson.

Rhonda L Stuart FRACP, PhD · Allen C Cheng FRACP, MPH, PhD · Caroline L Marshall FRACP, PhD, GradDipClinEpi · John K Ferguson FRACP, FRCPA, DTMH

The first rat I met in South Vietnam in 1967 was a hairless pup, jiggled by the tail in front of a bawling infant in a clinic we were holding in a refugee camp in sand dunes on the central coast, south of the city of Tuy Hoa. His mother had produced it from inside her shirt for tranquilising purposes, and it did the trick. As his eyes focused, the infant’s larynx relaxed, and everyone began to feel better until stubby hands groped for the rodent. With a twist of the wrist, however, the mother avoided a spectacle that might have lingered in our minds. I met my second rat later that day. He was a hairy thing, bolting across the sandy road between the barracks, and I wondered what he was doing out in the sun. I was surprised when he came to a sudden stop, and incredulous when he began to move backwards in a limb-whirling shower of sand. I blinked to clear my eyes of perspiration and found the reason for the rat’s reverse: fishing line connecting a rear leg to the hand of a small boy squatting with friends in the shade beside one of the huts. The rat was being reeled in to be released again, and yet again, by serious captors. I met more rats when I went into one of the barracks on a “home visit”. The huts were all the same, erected on the sand from corrugated iron and jammed with 30–40 people and their belongings. The inmates had been relocated from war zones for their own “good” and passed their days in idle misery, eating grain delivered by the government and throwing their refuse into open pits. It was very hot in the barracks — literally like being in an oven because each family cooked its meals over open fires, inside the tin sheds, in the sand dunes, under the blazing sun. The huts were stifling with smoke and humanity. I made my way to one fire to see what was on for lunch and found a frying pan filled with rats. Denuded, disembowelled and beheaded, they sizzled flank by flank under the care of an older woman in black pyjamas. Nearby lay the first of my patients: a man who was sick, febrile and immobilised by a large, painful lump in his groin, which was covered by oedematous, bluish skin. An abscess, I thought, and injected the only antibiotic I had, streptomycin, before moving to the next patient, who also had an abscess. And then, another. This seemed odd, but I remembered the holiday I had once endured as a small boy on a waterless farm in Queensland and the crops of boils that had erupted in the nether regions of several of us children after sharing an inch or two of black bath water. I suspected poor hygiene. It never crossed my mind the abscesses might have had something to do with the rats. But these “boils” were so large, and the people so sick, I aspirated one and sent pus to a nearby United States Air Force laboratory. Returning in a few days for the results, I had barely begun to savour the delicious air conditioning when a door was flung open and the technician announced with great excitement: “It is P. pestis! P. pestis! [Pasteurella pestis; now known as Yersinia pestis]” So what? I wondered, trying to recall any mention of that organism in my recent undergraduate experience at the University of Sydney. The technician informed me that we had discovered an outbreak of plague. Plague in Vietnam did not begin or end in our refugee camp. It was first recorded in 1898 in Nha Trang, south of Tuy Hoa, and the absence of any local name seemed to confirm its novelty.1 It was assumed it had been transported by ship from Hong Kong, where the Chinese epidemic had reached in 1894.1 In 1906, it was reported in Saigon (now Ho Chi Minh City), where it became endemic and caused about 1000 cases a year until the strict French administration managed to restrict it to about 25 cases a year in the 1930s. It increased again in the 1940s, during World War II. From 1962, however, the incidence in South Vietnam soared —5000–10 000 cases were reported annually until 1973,1,2 after which it fell. What caused this apparent outbreak? Where did it come from? Why did it stop? Marshall and colleagues denied an outbreak, stating it had been endemic since importation, and this notable increase merely reflected better identification by the increased numbers of doctors and laboratories associated with the Vietnam War.3 As confirmation of endemicity, they cited outbreaks in refugees and Viet Cong prisoners from regions beyond the reach of allied hospitals.3 Most rejected these denials but, if endemic, where was the fertile reservoir? Rural or town rats? It was argued “if there is no evidence that plague has come from outside sources” it must be based in “local wild rodents”,4 who transmit it either directly to humans, or indirectly, via urban rodents they have infected. Historically, plague has occasionally been associated with rural disruption. In India in 19945,6 and Algeria in 2003,7 outbreaks were preceded by rural earthquakes. Did burrows of rodents in rural areas collapse, forcing their residents to join — and infect — human refugees? Did broken buildings provide access to more food and permit proliferation? In South Vietnam, during the Vietnam War there were two massive disruptions in rural ecology: the bombing campaign and defoliation. Coincident with the outbreak of plague, 7.5 million tons of bombs (plus other ordnance) were dropped on rural South Vietnam: three times the weight dropped in World War II and with 100 times the combined impact of the atomic bombs dropped on Japan.8 Did these artificially made earthquakes drive rural rodents to the towns? Did they rupture grain stores, allowing access to food sources? Was there a limit to how much even a rat could take? Did defoliation alter their eating habits, with the same result? In 1962, Operation Ranch Hand was launched to deprive the Viet Cong of food and cover. It peaked in 1968–1969 and ended in 1971, after the spraying of over 6 million acres of rural land.9 Deforestation increases contact between humans and sylvatic sources,5 and Akiev noted that 86% of cases of plague in South Vietnam between 1966 and 1970 occurred in the most defoliated provinces.10 In many of these provinces, plague appeared for the first time. Although plausible, the theory that rural mammals were the source of plague was contradicted by field studies that found the disease to be surprisingly restricted to town mammals. Although trapping in the countryside was a dangerous pastime in those days, restricting research, Marshall and colleagues found that 99% of infected animals were the town rats, Rattus norvegicus, R. rattus, R. exulans, and the house shrew, Suncus murinus.11 After the war, researchers found that zoonotic foci were restricted to human settlement. Moreover, the flea vector, Xenopsylla cheopis, “exist[ed] only on indoor, commensal rodents”.12 Later, Suntsov and colleagues found only one rare flea to be common to rural and urban rodents, making it unlikely plague would be transferred from one to the other.13 If the rural mammals were not abandoning their homes, humans were. Around 3 million people (10% of the population) were relocated to camps such as ours in Tuy Hoa, and plague has long been recognised as a disease of the poor, crowded in slums where rats proliferate on rubbish.14 Certainly, there was inadequate disposal of rubbish in our camp, but proliferation of the urban rodents may have been even more encouraged by the practice of feeding refugees with grain shipped from central deposits and stored imperfectly in the camps in the provinces.3 This promoted transportation of rats from sites of endemicity and ensured they were well fed for reproduction. Perhaps eating habits further contributed to disease. Human skinners of infected camels15 and marmots have contracted plague through breaks in the skin, and consumers of undercooked meat have become infected.16 The former are likely to present with axillary buboes and the latter cervical, but our cases were predominantly inguinal, suggesting flea bites on the legs. Also, the rats I saw being cooked were more in danger of being over- than underdone. Fleas quickly abandon the cooling bodies of their dead hosts. I suspect the refugees in our camp were infected as they prepared the corpses for dinner. The weather affects the incidence of plague and our outbreak occurred in the drier months, as observed elsewhere. It is argued that eggs and larvae of fleas perish in the wet season.17 However, the onset of the wet can hardly explain the pattern of illness, restricted infectivity and low mortality in the outbreaks in Vietnam compared with historical accounts of other epidemics. In South Vietnam generally, the classic signs of the disease were observed: the bubonic form (after the Greek bubo, for groin), in which lymph nodes draining the infecting bite of the flea are severely affected in association with the usual systemic poisoning by gram-negative bacteria; the septicaemic form, in which the lymph nodes are not prominent; and the pneumonic form, in which bacteria invade the lungs and can be very infectious.3,18 In our outbreak, however, we only recognised the bubonic form, which also seems to have predominated in other regions. Despite the crowding in the barracks, we recognised no pneumonic forms or transference. Less common features of plague were also observed in Vietnam: asymptomatic pharyngeal carriage;19 pharyngitis and cervical adenopathy;20 and meningitis, particularly if undertreated21 — but we recognised none of these forms. Vietnam, however, did not conform to the historical concepts of expanding disaster. Many outbreaks were described, but they remained contained in numbers and sites. For example, we only recognised 15–20 patients with plague, and the disease did not spread to nearby camps or the city of Tuy Hoa; nor, mercifully, did any of our team become infected, despite the lack of any preventive measures. Early diagnosis and treatment was considered “the single most outstanding facet of plague control” in Vietnam, reducing the overall mortality to 1%–5%.3 Our practice of widespread injections of streptomycin, therefore, must have been blindly successful. We did not observe any deaths. Mass vaccination with live attenuated strains of some 10 million South Vietnamese would have contributed to control, but we did not even know this existed. Our public health management bore no responsibility for the containment of plague in our camp. There was none. Did the high ambient temperature inhibit spread? Infectivity in the flea is promoted by a “blockage” in the gut, which allows the bacteria to multiply before being regurgitated into the next host, but Cavanaugh and colleagues showed that blockage was reduced when the temperature of the flea exceeds 27.5°C, and I doubt our camp ever got below that temperature.1 Hinnebusch and colleagues found all fleas fail to block at temperatures greater than 30°C and, moreover, that their lifespan at that temperature is severely reduced, arguably due to dehydration.22 Perhaps the hot, dry environment in the camp, especially in the huts where rats were killed and prepared for food, restricted the passage of the disease by its effect on fleas. The outbreak from 1962 to 1973 was probably due to proliferation of rats and refugees and catalysed by recipes (that involved cooking rodents to prevent starvation), with the bombing and defoliation more a cause of human than rodent displacement. After the war, the reported incidence fell to several hundred cases annually until 1997, and to 22 in 2000.23 No cases have been reported since 2002.24 This progress may reflect better living conditions and patient care in Vietnam, but the natural history of plague has always been episodic, with the disease emerging and disappearing for reasons not understood.7 Pham and colleagues report a reduction in the number of rodents and fleas trapped in central Vietnam from 2000 to 2007, and absence of Y. pestis in both rats and fleas in recent years, and suggest that Vietnam may have entered one of the “silent period[s]” that have historically preceded “sudden explosions of rodent or human plague”.24 Although we did not observe any plague-related deaths in the epidemic in our camp, it might have been close. One night, feeling the need to give a sick child an extra injection (and, it must be confessed, to pursue adventure), three of us set out to visit the camp, which lay on the other side of a wide river, the Song Ba, beyond the security of the town. The road bridge had been destroyed and cars had to traverse the kilometre-long railway bridge on planks of wood that covered the sleepers, about 60 feet above the fast-flowing water. To add to the challenge, no one dared use headlights. We travelled in our old Land Rover whose gears were as disinclined to engage as the brakes, and whose muffler was as loud and steering as loose as the ladies in the “entertainment” area between the camp and the Air Force base. But when we arrived at the camp, and shut down the roaring engine, we were astonished by the silence and emptiness of the streets. It was a moonless night and we had difficulty in finding the right barrack, searching along the road with increasing dismay. The people were slow to open the door, and stood silently while we gave our needle. Firelight flickered on unsmiling faces. Just how “pacified” were these people? Let’s go! We held our breath until the car started and hurried back to the bridge to begin the slow, lurching crossing to safety. Then, about a quarter of the way across, a shape loomed from the darkness in front of us and a huge truck ground to a halt, followed by some others. We had run into an American convoy on its way to war. I was driving and, looking up, against the stars I could see the shape of a machine gunner hunched down upon us. There was a pause, with engines growling like dogs gearing for savagery; then Bruce Hansen, my team leader and good friend, swung open his door, bounded across the sleepers and pounded on the door of the truck, demanding they “back up” because “we were on the bridge first” and we were “Australians”. The driver of the truck did not take long to respond. A head appeared from above me with a simple message delivered with a southern drawl. Stripped of embellishments it was, “You back up right now, or I will push you off”, and it was confirmed by a roar of his engine and a lurch of his mighty truck. There were two practical problems with our gears: finding the right one and holding it in place. Crashing through several, I found reverse and, holding it in place, began the long, backward retreat. My leader maintained criticism of my cowardice — but from the safety of the sleepers. The machine gunner maintained his downward menace. I could have drowned like a rat. Would they have counted me a victim of plague? At least I would have been spared the injections. Boys in South Vietnam play with a lizard and rats, 1967. Reproduced from the Bruce Hansen Collection with permission of his widow, Miranda Hansen. The interior of one of the barracks in the refugee camp near Tuy Hoa, South Vietnam, 1967. Reproduced from the Bruce Hansen Collection with permission of his widow, Miranda Hansen.

John S Whitehall FRACP, MRCP(UK), DCH

Vaccinia vaccine is used to immunise against smallpox, which is caused by the orthopoxvirus, variola. A 26-year-old laboratory worker was inoculating mice with vaccinia vaccine as part of research into cross-reactivity among poxviruses. This particular vaccine contained a live attenuated strain of vaccinia (Western Reserve). The laboratory worker had himself received vaccinia vaccine in 2004 because of the nature of his work. On this occasion, after inoculating two mice, he suffered a needlestick injury to the left index finger. Two days later, a cloudy vesicle, typical of vaccinia virus,1 appeared at the inoculation site (Figure, arrow). After 3 more days, the finger became acutely inflamed, with secondary lymphangitis and axillary lymphadenitis. After antibacterial therapy, the lymphangitis and lymphadenitis rapidly resolved and the vesicle disappeared within 10 days. The man remains well. Infection with vaccinia usually follows vaccination or needlestick injuries. Although this is usually mild and self-limiting, certain conditions (eg, immunocompromise, pregnancy, eczema) predispose to more severe and even fatal illness. Prior immunisation with the vaccinia vaccine is thought to prevent or reduce the severity of such infections, and it is recommended that people working with vaccinia or related orthopoxviruses be vaccinated every 10 years.1 Vaccinia immunoglobulin and certain antiviral agents have been used to treat severe infections.2 Given the potential dangers from accidental exposure and the fact that the last documented case of smallpox (in 1978) was related to a laboratory incident,3 strict infection control measures are paramount, including disinfection after injury, prompt reporting, urgent medical review, and measures to minimise secondary spread to contacts.1

Sanjaya N Senanayake

We present the first clinical descriptions of immune-mediated paradoxical reactions to effective antibiotic treatment for Mycobacterium ulcerans infection, which result in clinical deterioration after initial improvement. Recognition of this phenomenon could prevent unnecessary changes to antibiotic regimens, and might obviate the need for, or reduce the extent of, further surgery. (MJA 2009; 191: 564-566) Clinical recordsPatient 1A 46-year-old man presented with a 3-month history of a slowly enlarging asymptomatic lesion on the lateral aspect of his right leg, that ulcerated and reached a size of 1.5 cm in diameter. A diagnosis of Mycobacterium ulcerans infection was confirmed by histopathological examination, which showed the classic appearance of a necrotic lesion involving the dermis and subcutaneous tissue, with a sparse acute inflammatory reaction, fat cell ghosts and large numbers of extracellular acid-fast bacilli (AFB)1 (Box, A and Box, B). In addition, culture and polymerase chain reaction (PCR) tests of excised tissue were positive for M. ulcerans. The ulcer was excised with primary skin closure and clear histological margins, and adjunctive antibiotic therapy (with 300 mg rifampicin and 500 mg ciprofloxacin, twice daily) was commenced with a planned duration of 3 months. This lesion had not recurred in the ensuing 7 months. However, in the 2 days before the first lesion was treated, the patient spontaneously developed, proximally, an area of erythema and swelling over the right knee. Although secondary M. ulcerans infection at the site was considered, bacterial cellulitis or bursitis was possible, so it was decided to observe the response to intravenous therapy with cephazolin. Initially, the amount of induration and erythema decreased significantly, but did not resolve completely. About 5 weeks later, the area became increasingly inflamed and, over the following month, became fluctuant but not ulcerative. An aspirate of the lesion confirmed the presence of M. ulcerans with AFB seen on microscopy, and a positive M. ulcerans PCR. The patient, therefore, underwent further wide excision of the lesion with a split-thickness skin graft. The antibiotic regimen was changed by replacing ciprofloxacin with clarithromycin (500 mg twice daily) while continuing with rifampicin. Histopathological examination of the excised tissue showed extensive undermining necrosis in the fat and subcutaneous tissue, accompanied by a florid mixed inflammatory reaction with multinucleated giant cells (Box, C). However, only a few sparse AFB were seen (Box, D). Mycobacterial cultures of the aspirate and the excised tissue were negative at two separate laboratories. The patient completed a further 7 weeks of postoperative antibiotic therapy and, after 6 months, there was no evidence of further M. ulcerans lesions. Patient 2A 66-year-old man presented with a 6-week history of a painless ulcer on the left elbow, with significant surrounding induration. A diagnosis of M. ulcerans infection was made, and antibiotic therapy (300 mg rifampicin and 500 mg ciprofloxacin, twice daily) was commenced. One week later, a wide excision and split-thickness skin graft was performed, although not all the indurated area was excised. Culture and PCR of excised tissue was positive for M. ulcerans. Histopathological examination of the excised lesion showed classic features of M. ulcerans infection, with necrosis of the dermis and subcutaneous tissue, a limited and focal inflammatory response, and large numbers of extracellular AFB. These changes extended to the deep excision margin. The clinical appearance of the indurated area that was not excised improved significantly after surgery. However, 6 weeks later and while still taking the antibiotics, over 48 hours, the patient developed erythema and induration of the left elbow region that extended inferiorly from the lower edge of the excisional wound onto the forearm; the condition had the clinical appearance of cellulitis. This was thought to be a secondary bacterial infection, but it worsened despite intravenous therapy with cephazolin. The patient, therefore, underwent further operative exploration, during which extensive liquefied fat extending distally into the forearm was found and debrided. Histopathological examination of excised tissue showed inflamed granulation tissue with lymphocytes, histiocytes and occasional multinucleated giant cells, and scattered necrotic foci. There were no AFB detected on microscopy and, although PCR of the tissue was positive, cultures were negative for M. ulcerans. The antibiotic regimen was changed by replacing rifampicin with clarithromycin (500 mg twice daily), and the patient took clarithromycin for a further 3 months and ciprofloxacin for a further month. The wound healed completely by secondary intention, and there has been no evidence of recurrence of M. ulcerans infection 10 months after the second operation. DiscussionA “paradoxical” reaction describes a deteriorating response to treatment of an infection after initial improvement.2 Such reactions have frequently been described in infections with a number of mycobacterial species, including those causing tuberculosis, avium-intracellulare complex and leprosy, and although they occur most commonly in severely immunosuppressed patients with HIV/AIDS who are undergoing antiretroviral therapy, they can occur in immunocompetent hosts.2,3 The pathogenesis relates to an enhanced immune response to mycobacterial antigens on treatment that produces deleterious clinical effects.1 Its immune basis means that this phenomenon is also referred to as “immune reconstitution syndrome”. M. ulcerans causes necrotising lesions of skin and subcutaneous tissue. Despite large numbers of extracellular mycobacteria, lesions are characterised by a poor inflammatory response.4 This is probably induced by immuno-inhibitory characteristics of mycolactone, the exotoxin produced by M. ulcerans,5,6 which plays a crucial role in the pathogenesis of infection with this organism. Treatment primarily involves surgical excision; however, recent evidence has shown that antibiotics can have an effective role,7,8 and their use is now recommended.9,10 Clinical paradoxical reactions during the treatment of M. ulcerans have not been previously described. Clinical deterioration during antibiotic treatment can be interpreted as treatment failure, leading to further expensive and potentially disfiguring surgery, and a change in antibiotic regimens or a prolongation of their use. In the two cases we describe, involving treatment of M. ulcerans infections in patients from an endemic area in the Bellarine Peninsula of south-eastern Australia,7 initial improvement during antibiotic therapy was followed by a paradoxical worsening in the clinical appearance. This was first interpreted as treatment failure, but we believe it was subsequently shown to result from an immune-mediated reaction to effective antibiotic treatment. We feel that in Patient 1, the lesion on the right knee represented a secondary M. ulcerans infection that was present at the time the lower right leg lesion was treated. It showed initial improvement with antibiotic therapy, but there was subsequent clinical deterioration consistent with a paradoxical reaction to mycobacterial antigens at the site. Likewise, in Patient 2, the clinical postoperative deterioration at the wound margins after initial improvement in an area of incomplete excision of the mycobacterial infection represented a paradoxical reaction to remaining mycobacterial antigens. To our knowledge, these are the first clinical case reports describing paradoxical reactions during the treatment of M. ulcerans. There is published histological evidence to support M. ulcerans-associated paradoxical reactions in patients being treated with antibiotics. Antibiotic therapy for M. ulcerans has been shown to lead to an apparent reversal of the immune-tolerant state of active M. ulcerans infection, with phagocytosis of mycobacteria and a rapid onset of local cellular immune responses.1 These responses are characterised by the formation of epithelioid granuloma with multinucleated giant cells and large clusters of lymphocytes. It is likely that antibiotics facilitate this immune reaction by reducing the production of the immuno-inhibitory exotoxin mycolactone,1 and also by liberating mycobacterial antigens from dead organisms. The evidence for a paradoxical reaction in our cases included: (i) persisting M. ulcerans organisms in affected tissue after the initial surgery; (ii) an initial clinical improvement in the M. ulcerans lesions during antibiotic therapy, followed by significant clinical deterioration 1–2 months after antibiotic therapy was commenced; (iii) negative cultures from aspirates and excised tissue, suggesting that remaining mycobacteria were not alive as would be expected in a lesion that was worsening as a result of uncontrolled infection; (iv) the lack of mycobacteria seen on microscopy of the excised tissue, compared with active lesions that usually show large numbers of extracellular mycobacteria;4 and (v) significant inflammatory reactions evident on histopathological examination of excised tissue, in contrast to what was observed in the initial active lesions, and consistent with recent descriptions of immune responses in successfully treated M. ulcerans infections.1 Thus, we propose that rather than progression of the lesions because of failure of antibiotic treatment, these cases represent an adverse consequence of effective antibiotic treatment. By applying lessons learnt from the management of immune-mediated reactions to infections with Mycobacterium tuberculosis,2 the recognition of paradoxical reactions during treatment of M. ulcerans infections might significantly influence the management of these infections. First, rather than ceasing the antibiotic therapy or changing the regimen, we advocate that therapy be continued, and that it not be changed unless there is evidence of antibiotic failure on histopathological examination or culture. Further, prolongation of the intended duration of antibiotic therapy is probably not required. Second, it may be possible that repeated needle aspiration for fluctuant lesions, as we described in Patient 1, may be effective in settling the lesion. This has been shown for lesions caused by M. tuberculosis,11 and would avoid further surgery, which, in Patient 1, included costly and disfiguring skin grafts. Finally, adjunctive corticosteroid therapy may help to settle the lesion and obviate the need for, or reduce the extent of, surgical intervention.12 We feel that the descriptions of these cases are important, as they can alert clinicians to the possibility of paradoxical reactions occurring during antibiotic treatment for M. ulcerans. We recommend that when initial improvement on antibiotic treatment is followed by clinical deterioration of lesion, clinicians perform histopathological examination and mycobacterial culture of involved tissue to assess the possibility of a paradoxical reaction. Lesions in Patient 1 First lesion, before antibiotic treatment showing: (A) a sparse acute inflammatory reaction around necrotic fat and subcutaneous tissue (haematoxylin and eosin stain; original magnification, ×100 ; and (B) high numbers of extracellular acid-fast bacilli (pink) on Wade–Fite stain (original magnification, × 400). Second lesion after 11 weeks of antibiotic treatment showing: (C) a dense inflammatory reaction including multinucleated giant cells (haematoxylin and eosin stain; original magnification, ×100; and (D) only one small cluster of extracellular acid-fast bacilli on Wade–Fite stain (original magnification, × 400).

Daniel P O’Brien MB BS, FRACP · Michael E Robson MB BS, FRCPA · Peter P Callan MB BS, FRACS · Anthony H McDonald MB BS, FRACS

To the Editor: Hospitalisation rates for seasonal influenza are highest among young children and people aged over 65 years.1-3 Calculation of laboratory-confirmed infection rates is difficult because influenza testing is not consistently performed. Using diagnostic codes to identify hospitalisations for acute respiratory illness provides one measure of the relative burden of pandemic (H1N1) 2009 (pH1N1) virus infection compared with influenza virus infections in previous influenza seasons. On 26 May 2009, the first pH1N1 virus human infection in New South Wales was identified, and between June and August 2009, pH1N1 was the predominant circulating influenza virus strain (found in 15%–82% of influenza A-positive specimens).4 In July 2009, the Hunter New England Area Health Service (HNEAHS) (population, 866 000) in NSW established population-based surveillance for hospitalisations for acute respiratory illness at all 35 HNE public hospitals admitting patients with respiratory illness. Data on hospitalisations coded with eight International Classification of Diseases (10th revision) codes (Box 1) were analysed by age group and year. Data for 2007 and 2008 (relatively severe and relatively mild influenza seasons, respectively)5 were used for comparison. Monthly hospitalisation rates for acute respiratory illness were calculated for 1 January 2007 to 31 August 2009. Over the period June to August in 2007 and 2008, 1736 and 1267 hospitalisations for acute respiratory illness occurred, respectively, and monthly hospitalisation rates peaked during August in both years (859 [9.7/10 000 persons] in 2007 and 517 [5.8/10 000 persons] in 2008). The highest hospitalisation rates occurred in children aged 0–4 years (113 [20.6/10 000 persons] in 2007 and 37 [8.9/10 000 persons] in 2008) and in people aged ≥ 62 years (276 [16.3/10 000 persons] in 2007 and 212 [12.1/10 000 persons] in 2008). In 2009, over the same 3-month period (June to August), there were 2378 hospitalisations for acute respiratory illness, with monthly hospitalisation rates peaking in July (1029 [11.4/10 000 persons]). Between May 2009 (before pH1N1 circulation) and July 2009, the monthly hospitalisation rate for acute respiratory illness in the HNEAHS increased by 260% (from 385 [4.3/10 000 persons] to 1029 [11.4/10 000 persons]). During the same period, age-specific hospitalisation rates increased more than threefold among children aged 0–4 years (from 31 [5.5/10 000 persons] to 101 [17.9/10 000 persons]) and 5–16 years (from 36 [2.5/10 000 persons] to 140 [9.8/10 000 persons]), and more than sixfold among people aged 17–31 years (from 43 [2.6/10 000 persons] to 281 [16.9/10 000 persons]) (Box 2). In July 2009, age-specific hospitalisation rates among people aged 5–61 years exceeded respective peak age-specific hospitalisation rates for 2007, while hospitalisation rates among children aged 0–4 years and people aged ≥ 62 years remained below 2007 peak rates for their respective age groups. Although our analysis calculated hospitalisation rates for various types of respiratory illness (including infections with non-influenza viruses) and may be affected by changes in health care-seeking behaviour and coding practices, comparison over multiple seasons suggests several unique features of the 2009 influenza season in the HNE region. Compared with 2007 and 2008, the HNEAHS experienced a rapid, early increase in hospitalisations for acute respiratory illness, coinciding with the emergence of pH1N1. Furthermore, a disproportionate burden of hospitalisations occurred among people aged 5–61 years (particularly those aged 17–31 years), with a relatively lower burden among those aged ≥ 62 years. Ongoing surveillance will determine whether these age-specific trends continue in the 2010 influenza season. 1 Emergency department ICD-10 separation codes used for acute respiratory illness hospitalisation surveillance Code Disease J11 Influenza, virus not identified J11.1 Influenza with other respiratory manifestations, virus not identified J11.8 Influenza with other manifestations, virus not identified J12.9 Viral pneumonia, unspecified J15.9 Bacterial pneumonia, unspecified J18.9 Pneumonia, unspecified J22 Unspecified acute lower respiratory infection J96.9 Respiratory failure, unspecified ICD-10 = International Classification of Diseases (10th revision). 2 Monthly hospitalisation rates for acute respiratory illness in the Hunter New England Area Health Service region, May–August 2009, compared with peak monthly rates in 2007 and 2008* * Hospitalisation rates are per 10 000 residents of the Hunter New England Area Health Service region.

Fatimah S Dawood · Craig B Dalton · David N Durrheim · Kirsty G Hope

Objective: Design and setting: Prospective modelling with the tools FluSurge 2.0 and FluAid 2.0 (developed by the United States Centers for Disease Control and Prevention) over 12 weeks from when the pandemic “Contain” Phase was declared on 22 May 2009, compared with data obtained from daily hospital reports of pandemic (H1N1) 2009 influenza-related admissions and transfers to intensive care units (ICUs).Main outcome measures: The effect on hospitals as projected by the FluAid 2.0 model compared with observed hospital admissions and ICU admissions.Results: Prospective use of the FluAid 2.0 model provided valuable health intelligence for assessment and projection of hospitalisation and critical care demand through the first 10 weeks of the pandemic in Victoria. The observed rate of hospital admissions for pandemic (H1N1) 2009 was broadly consistent with a 5% gross clinical attack rate, with 0.3% of infected patients being hospitalised. Transfers to ICUs occurred at a rate of 20% of hospital admissions, and were associated with vulnerable patient groups, and severe respiratory failure in 82% of patients admitted to ICUs. Most patients treated in ICUs (85%) survived after an average ICU length of stay of 9 days (SD, 6.5 days). Mechanical ventilation was required by 72% of patients admitted to ICUs, and extracorporeal membrane oxygenation (ECMO) was used for 7%. Pre-existing haematological malignancy accounted for half of all the deaths in patients admitted to ICUs with pandemic (H1N1) 2009 influenza.Conclusions: Prospective use of modelling tools informed critical decisions in the planning and management of the pandemic. Early estimation of the clinical attack rate, hospitalisation rates, and demand for ICU beds guided implementation of surge capacity. ECMO emerged as an important treatment modality for pandemic (H1N1) 2009 influenza, and will be an important consideration for future pandemic planning.

Martin E Lum MB ChB, FANZCA, MBA(Exec) · Alison J McMillan CCN, BEd, MBA · Chris W Brook FRACP, FAFPHM, FRACMA · Rosemary Lester MPH, MS(Epid), FAFPHM · Leonard S Piers MD, PhD, MPH

Standard and Droplet Precautions are considered adequate to control the transmission of influenza in most health care situations. Vaccination of health care staff, carers and vulnerable patients against seasonal and, eventually, pandemic influenza strains is an essential protective strategy. Management principles include: performance of hand hygiene before and after every patient contact or contact with the patient environment, in accord with the national 5 Moments for Hand Hygiene Standard; disinfection of the patient environment; early identification and isolation of patients with suspected or proven influenza; adoption of a greater minimum distance of patient separation (2 metres) than previously recommended; use of a surgical mask and eye protection for personal protection on entry to infectious areas or within 2 metres of an infectious patient; contact tracing for patient and health care staff and restriction of prophylactic antivirals mainly to those at high risk of severe disease; in high aerosol-risk settings, use of particulate mask, eye protection, impervious long-sleeved gown, and gloves donned in that sequence and removed in reverse sequence, avoiding self-contamination; exclusion of symptomatic staff from the workplace until criteria for non-infectious status are met; reserving negative-pressure ventilation rooms (if available) for intensive care patients, especially those receiving non-invasive ventilation; ensuring that infectious postpartum women wear surgical masks when caring for their newborn infants and practise strict hand hygiene; and implementation of special arrangements for potentially infected newborns who require nursery or intensive care.

Rhonda L Stuart FRACP, PhD · Allen C Cheng FRACP, MPH, PhD · Caroline L Marshall FRACP, PhD, GradDipClinEpi · John K Ferguson FRACP, FRCPA, DTMH

Mandatory reporting and public sharing of information would likely lead to improved health care practices and save lives Staphylococcus aureus bacteraemia (SAB) is common, and it causes serious morbidity and mortality. In Australia, it is estimated that there are over 6000 episodes per year, most of which are health care-associated.1 SAB is also a major problem internationally, and this problem is compounded by antibiotic resistance. Methicillin-resistant S. aureus (MRSA) infections are common in most countries, and MRSA bacteraemia has reached epidemic proportions in some areas of the United States.2,3 The study by Turnidge and colleagues on behalf of the Australia New Zealand Cooperative on Outcomes in Staphylococcal Sepsis in this issue of the Journal4 highlights again how frequently these infections occur, their association with health care (particularly with intravascular catheters), and the high mortality rate associated with them (over 20% by 30 days). It also illustrates our rapidly growing problem with community MRSA strains, which caused over 6% of all the SABs in the period June 2007 to May 2008, during which Turnidge et al collected data. Currently, we have only very patchy measurements of this problem in Australia in comparison with New Zealand, Denmark and the United Kingdom,2 where all SABs are measured. Despite probably causing more deaths in Australia than occur on our roads, there is very little investigation into the causes and the preventable factors of individual episodes of bacteraemia. Most of these infections are preventable. Numerous interventions (such as compliance with hand hygiene and improved care of intravenous catheters) have been shown to lead to major reductions in rates of bacteraemia.2,5,6 The current National Hand Hygiene Initiative7 should also achieve a significant reduction. The Australian Commission on Safety and Quality in Health Care has noted how significant these infections are, and the importance of surveillance.2 It has also taken this matter to the Australian Health Ministers’ Conference, which then endorsed the reporting of SABs in each jurisdiction and nationally. It is time that all health care facilities started collecting and acting on information about SABs. However, this probably won’t happen effectively unless all SABs (based on pathology laboratory results) are made “reportable”. After mandatory reporting was introduced in the UK, the number of documented cases increased by 50%.2,8 It is important that we do more than just collect these data. We need to ensure that, in each hospital, every case is looked at to try to determine why it occurred. Then health care professionals need to intervene at their own local level to make sure that appropriate policies are adhered to (or, where necessary, changed). Nearly all people with SABs are either in hospital already, or will be admitted. Thus, it should be possible to see them at or near the time of their infection. This will usually mean that either a physician or an infection control practitioner would look at every case to determine whether it was the result of a health care-associated procedure, and also look into other issues, such as the likely cause (eg, intravascular catheter) and outcomes.2 This would then also allow timely feedback to the teams responsible for the patients’ current and previous medical care about potential preventable factors.9 Many episodes of SAB, even though they are health care-associated, have their onset in the community. Thus, all cases of SAB will need to be looked at, and not just those with their onset in hospitals.1,2,9 While this will seem arduous to some, at the Canberra and Austin Hospitals, it takes between 30 and 60 minutes to see each affected patient and review each case.2,9,10 Even our largest hospitals are unlikely to have more than a couple of hundred SAB episodes per year. As these episodes have a mortality of more than 20%, this is not an undue task to expect hospitals to perform. They need to devote resources to doing this, and make it part of the core duties of any infection control team. It is important that the data be analysed, reported and acted on in a timely fashion, and this process must involve those at the hospital executive level. The success and benefits of doing this at a local level are highlighted in the study reported by Dendle and colleagues in this issue of the Journal.10 The study by Turnidge et al shows how data can be analysed and reported efficiently at a national (and international) level, with relatively few extra resources being supplied, through the use of a web-based tool.4 Such a system allows summaries to be sent back to the individual hospitals so that they can look at their own data in a timely fashion. It also allows some external auditing of the data to ensure they are accurate. Importantly, it will allow hospitals of similar types to benchmark themselves nationally. This is important because we already know that hospitals in Perth have much lower rates of health care-acquired MRSA than those in the eastern states,11 and we should learn from them. Most Australian states do not have sufficiently large populations to make many comparisons internally, especially of their largest hospitals, where most cases of SAB occur. By using national comparisons, institutions with higher rates of infections should be able to learn from those that have lower rates of infections. There are always arguments that looking at these data and having them publicly available does not help. However, the experience in the UK suggests otherwise. Amid controversy, SAB rates have been published on the web for many years, and this type of benchmarking, when coupled with funded infection control interventions, has led to a 50% reduction in the number of MRSA bacteraemias.2,8 This has not only resulted in substantial monetary savings, but, more importantly, has saved many hundreds of lives each year. Internationally, we are seeing rising levels of SAB. This is principally the result of complications of health care, and most of these infections are preventable. It is time we measured these life-threatening episodes much more accurately, examined each case, and intervened to stop further cases occurring.

Peter J Collignon FASM, FRCPA, FRACP · Marilyn Cruickshank RN, PhD, FRCNA

Objective: To document the types of, and mortality from, Staphylococcus aureus bacteraemia in Australia and New Zealand, and determine factors associated with mortality.Design and setting: Prospective observational study in 27 independent or hospital pathology laboratories in Australia (24) and New Zealand (3), employing a web-based database to prospectively record demographic features, selected risk factors, principal antibiotic treatment and mortality data on all patients with positive blood cultures for S. aureus from June 2007 to May 2008.Main outcome measure: 30-day all-cause mortality.Results: 1994 episodes of S. aureus bacteraemia were identified, and complete 30-day follow-up data were available for 1865. Most episodes had their onset in the community (60.8%; 95% CI, 58.7%–63.0%). Methicillin-resistant S. aureus (MRSA) caused 450 episodes (24.1%; 95% CI, 22.2%–25.9%), and 123 of these (27.3%) had a susceptibility profile consistent with community-associated MRSA. All-cause mortality at 30 days was 20.6% (95% CI, 18.8%–22.5%). On univariate analysis, increased mortality was significantly associated with older age, European ethnicity, MRSA infection, infections not originating from a medical device, sepsis syndrome, pneumonia/empyema, and treatment with a glycopeptide or other non-β-lactam antibiotic. On multivariable analysis, independent predictors of mortality were age, sepsis syndrome, pneumonia/empyema, device-associated infection with a secondary focus, left-sided endocarditis, and treatment with a glycopeptide such as vancomycin, but not MRSA infection.Conclusions: S. aureus bacteraemia is a common infection in both the community and hospitals in Australia and New Zealand, and is associated with appreciable mortality. Invasive MRSA infection may be more life-threatening, partly because of the inferior efficacy of the standard treatment, vancomycin. National web-based surveillance of S. aureus bacteraemia and its outcomes is not only important but also easily achievable.

John D Turnidge FRACP, FRCPA, MASM · Despina Kotsanas BSc(Hons), MClinEpi · Wendy Munckhof FRACP, FRCPA, PhD · Sally Roberts MB ChB, FRACP, FRCPA · Catherine M Bennett BSc(Hons), MAppEpid, PhD · Graeme R Nimmo MPH, FRCPA, FASM · Geoffrey W Coombs BApplSci(Med Sci), PostGradDipMedSci · Ronan J Murray MRCPI, FRACP, FRCPA · Benjamin Howden MB BS, FRACP, FRCPA · Paul D R Johnson MB BS, PhD, FRACP · Kate Dowling BSc, GradDip(AppStats) · on behalf of the Australia New Zealand Cooperative on Outcomes in Staphylococcal Sepsis

Objective: To evaluate the practicality and effectiveness of a new program that made health care-associated Staphylococcus aureus bacteraemia (SAB) a quality indicator at Austin Health.Design and setting: Roll-out of the program over 9 months and review over 27 months from January 2006. Every episode of SAB at Austin Health was promptly reviewed, and classified as community- or health care-associated and as inpatient- or non-inpatient-related. Feedback was provided to treating clinicians for every SAB episode considered potentially preventable, and education-based interventions were introduced where appropriate.Main outcome measure: Episodes of SAB associated with health care at Austin Health per 1000 separations (hospital discharges) per month.Results: We identified 131 episodes of health care-associated SAB, of which 90 (68.7%) were caused by methicillin-susceptible S. aureus, 96 (73.3%) occurred in inpatients, and 65 (49.6%) were associated with a vascular access device. The health care-associated SAB rate was 1.1 per 1000 separations in the first 9 months, and fell by 55% to 0.51 per 1000 separations in the subsequent 18 months. We estimated that there were 80 fewer SAB episodes (95% CI, 20–140) than expected had the initial rate remained unchanged, a notional saving of $1.75 million to Austin Health over 27 months. About 16 hours per month of clinical nurse consultant time was required to maintain the program, representing a 0.1 equivalent full-time position, or a cost of $7000–$9000 per year.Conclusion: Introducing a structured program to investigate all health care-associated SABs, rather than only infections with methicillin-resistant S. aureus, revealed a large under-recognised burden of potentially preventable infections. The program was simple and low-cost, and the rate of health care-associated SAB has fallen significantly since its introduction.

Claire Dendle MB BS, FRACP · Rhea D Martin RN, MPH · Donna R Cameron RN, BAppSci · Elizabeth A Grabsch BSc, MPH · Barrie C Mayall FRACP, FRCPA · M Lindsay Grayson FRACP, FAFPHM · Paul D R Johnson FRACP, PhD

Objective: To describe a prolonged outbreak of mumps in the Kimberley region of Western Australia in 2007–2008.Design: Descriptive analysis of all mumps cases notified to the WA Notifiable Infectious Diseases Database for the period 1 July 2007 to 30 June 2008.Main outcome measures: Notified cases of mumps by patients’ place of residence, age, Indigenous or non-Indigenous ethnicity, vaccination status and method of diagnosis.Results: 84% (153/183) of mumps notifications in WA over the study period occurred in the Kimberley region or were directly linked to Kimberley cases. Median age of patients was 18 years (range, 2–63 years), and 54% of patients were aged less than 20 years. Almost all (92%) were Australian Aboriginal people; 67% (102/153) had received at least one dose of mumps vaccine, and 52% had received two doses. The highest notification rate (1816 cases per 100 000 population) was in the Aboriginal 15–19-years age group, and 92% of these patients had received at least one dose of mumps vaccine. Almost all outbreak cases (94%) were laboratory confirmed. Genotyping was performed on 20 mumps virus isolates: all were genotype J.Conclusion: A prolonged outbreak of mumps occurred in a well defined, highly vaccinated, predominantly young Aboriginal population in the remote Kimberley region of WA. This outbreak raises questions about the effectiveness and scheduling of the current vaccine (which is genotype A-derived), especially for Aboriginal people. Surveillance of circulating mumps virus genotypes and neutralisation studies will help in evaluating the protection provided by the current vaccine against genotypically different strains.

Revle D Bangor-Jones MB BCh, MRCGP, MPH · Gary K Dowse BMedSc(Hons), MSc, FAFPHM · Carolien M Giele BSc(Hons), MPH, GradDipClinEpi · Paul G van Buynder MB BS, MPH, FAFPHM · Meredith M Hodge MB BS, MPHTM, FRACP · Mary M Whitty RN, RM, ChildHlthCert

To the Editor: The Therapeutic Goods Association (TGA) has informed Australian eye banks that nucleic acid testing (NAT) of donor sera will be required in addition to routine serological tests for hepatitis B virus (HBV), hepatitis C virus (HCV) and HIV. NAT can detect viral genome in the window period between infection and the appearance of antigen or antibody, and is to commence in Australia as soon as possible. However, we believe the benefit of NAT would be small and the cost considerable. Importantly, it would be likely to have an adverse effect on the availability of donor corneas for transplantation. HBV, HCV or HIV have not been transmitted from seronegative donors by means of corneal transplantation. In the mid 1980s, HBV was almost certainly transmitted by corneal tissue to two recipients in the United States who developed acute hepatitis B; HBV surface antigen was detected subsequently in the donor sera.1 The transmission of HCV or HIV has not been reported despite corneal transplantation from infected donors.2,3 The American Red Cross instigated HCV/HIV (but not HBV) NAT for blood donors in 1999, and the US Food and Drug Administration mandated HCV/HIV NAT for eye donors in 2007. So, how many window-period eye donors could be identified by NAT? It has been estimated that 7.2 per 100 000 American tissue donors are in this period for HBV, HCV or HIV.4 With NAT, the number reduced to 1.8 per 100 000 (most assays, including NAT, have sensitivity limitations). Let us assume that the prevalences of HBV and HCV are the same in Australia and the US, the prevalence of HIV in Australia is half that of the US, and that prescreening by medical and social history is equally effective in both countries. At 700 corneal donors (1200 grafts) per year in Australia, one window-period donor would be expected every 23 years, falling to one every 93 years with NAT. Thus, one window-period donor would be detected by NAT every 30 years at an estimated cost of $9 million ($50 per donor averaged up for out-of-hours testing and kit wastage) plus any charges for specimen transport. If only HCV/HIV NAT is performed, such a donor would be detected every 52 years. What is the actual risk of infection? Assuming 25 000 corneal donors (43 000 grafts) per year in the US, the figures4 suggest that eyes were collected from one window-period donor every 7 months between 1990 (when a serological test for HCV became available) and 2007, but no infections have been reported. Perhaps there was no virus in the corneal tissue; even among donors who are seropositive for HBV, HCV or HIV, few have detectable viral genome in the cornea.5,6 It is not known whether these viruses can invade the cornea before the appearance of antibody, but the risk that infection will occur in recipients of corneas from HCV/HIV-seronegative, NAT-positive donors appears to be very small indeed. The TGA’s decision may have been based on factors other than this type of analysis. We believe the decision should be reconsidered.

Paul R Badenoch · Douglas J Coster

To the Editor: Italiano and colleagues described a 49-year-old woman with prolonged vaccine viraemia, associated with hepatitis, streptococcal toxic shock syndrome and poststreptococcal reactive arthritis following routine varicella vaccination.1 The woman, initially seronegative for varicella zoster virus (VZV), was stated to be immunocompetent, possibly because she was previously well and produced varicella IgG following vaccination. It is not clear whether other aspects of her immune status were investigated. Although VZV IgG was detected after vaccination, indicating appropriate adaptive immune activation, this does not necessarily exclude a defect in the innate immune system. Natural killer (NK) cells, which comprise 10%–15% of total lymphocytes, are part of the innate immune system and play an important role in the suppression of VZV replication via direct cell killing and production of γ-interferon.2,3 A smaller population of lymphocytes, known as NKT cells, which express both NK cell surface markers and T-cell receptors, also appear be important in controlling VZV infection in humans.2 The role of these cells in the immune response to varicella vaccine is unclear. In children, NK cell cytotoxicity increased after wild-type VZV infection but not after vaccine administration.4 However, disseminated life-threatening VZV infection was observed after varicella vaccination in a child with NKT cell deficiency.2 Primary isolated deficiencies and functional defects in NK function have been reported in children and adolescents with severe, life-threatening wild-type VZV infection.5 Some of these patients were previously well and came to medical attention only after VZV exposure. It is not clear how many had prior varicella vaccination, but at least one patient had previously received VZV vaccine with no adverse consequences and developed disseminated disease only with the wild-type virus. Acquired defects in NK immunity have also been reported. Severe transient depressions of NK and CD8 cell numbers and NK cell function have been documented in children at the time of severe VZV infection, with return of immune competence following convalescence.3 This phenomenon may be due to initial CD8 and NK cell exhaustion or redistribution of these cells from the circulation into inflamed peripheral tissue under the influence of chemokines.3 It has been suggested that an NK cell defect should be considered in unexplained severe herpesvirus infections.5 It would therefore be of interest to determine NK cell number and function and NKT cell number in the patient reported by Italiano and colleagues.

Sam S Mehr · Andrew S Kemp

To the Editor: I read with interest the recent case report by Lim and colleagues on Chromobacterium violaceum endocarditis.1 References to the article do not include a report of a similar case published 20 years ago, also in the MJA.2 Perhaps reference searches can be enhanced — otherwise, identifying such similar cases falls to recollected experience (I was the initial treating doctor in the 1988 case) or an improbably capacious memory in the author or reader. What saved the patient in February 19882 were two new antibiotics that were not generally available at the time but were held at Royal Brisbane Hospital — imipenem and ciprofloxacin. Imipenem is a β-lactam antibiotic of the carbapenem subgroup, derived from Streptomyces cattleya, that was developed in 1985.3 Imipenem and other carbapenems including meropenem, as used to treat the patient in the article by Lim et al,1 are now available in Australia but restricted to intravenous use in hospitals. The oral antibiotic ciprofloxacin became generally available with a Pharmaceutical Benefits Scheme authority benefit soon after the 1988 case. I recall a discussion at that time with the late Dr Richard Kemp (then Director of Infectious Diseases at Royal Brisbane Hospital), who told me that C. violaceum infection in humans had been described in the world medical literature only about 10 times, and there had been no eventual survivors. From a general practitioner’s perspective, there was a lesson to be learned from the case: take the time to swab an abscess. The one in question was unusual — volcanic in appearance, indurated and not productive of pus on incision.

Richard N Pearson

The wisdom of whores. Bureaucrats, brothels, and the business of AIDS. Elizabeth Pisani. Sydney: Granta, 2008 (xvii + 372 pp). ISBN 978 1 84708 024 0. Given the provocative cover, I approached this book with reservations. And irritatingly, the author scatters the terms “AIDS mafia” and “AIDS industry” throughout the book. She never defines the terms, but she would probably class me as a member of both! Yet after two careful readings, I am totally disarmed. While I disagree on some points, Elizabeth Pisani tells the truth about AIDS clearly and unequivocally. Only global warming is more topical than HIV/AIDS. Any thinking person, lay or professional, must have serious questions. Why is the epidemic in sub-Saharan Africa so different from everywhere else? Why has the long-awaited Grim Reaper scenario (spreading throughout the general community) never eventuated? Why, with a virus which is “not actually all that infectious” but which has nonetheless caused 70 million infections world-wide, are we no nearer to controlling the epidemic? Pisani answers these questions with devastating clarity. She is eminently qualified to do so, with a PhD in epidemiology and more than 10 years’ field experience. She retains, too, the sharpness and ruthlessness of the investigative journalist she once was. There are ribald stories and humour here, but throughout runs a barely repressed strain of anger. Bucket-loads of money are being wasted, good science is often ignored, truth has been replaced by lies and, as the author reminds us, prevention “programs based on lies don’t work”. There is a softer side to this author. She is a friend of harlots and sinners. It is people considered the dregs of society who are most at risk. She says, “Getting HIV prevention services for people who needed them most has begun to seem like a debt I owe”. By her forthright analysis and outline of what needs to be done, she has gone some way towards paying her debt.

David L Bradford

Objective: To describe demographic and clinical characteristics of patients residing in Victoria who were diagnosed with multidrug-resistant tuberculosis (MDR-TB) during the period 1 January 1998 to 31 December 2007.Design, setting and patients: Retrospective review of Victorian Department of Health data on laboratory-confirmed cases of MDR-TB for the period 1998–2007.Main outcome measures: Age, sex, country of birth, time between arrival in Australia and notification of TB, residency status, site of disease, and treatment period and outcome.Results: From 1998 to 2007, 31 patients who resided in Victoria were diagnosed with MDR-TB. The median age of patients was 27 years, most patients were born overseas, and more than half were full-time students. The median time between arrival in Australia and notification of TB was 2 years, and 24 patients were notified to the Department within 5 years of arrival. Twenty patients had pulmonary disease; in 12 of these patients, sputum was smear-positive for acid-fast bacilli. The median treatment period for patients who completed treatment was 22 months.Conclusions: The number of patients diagnosed with MDR-TB per year increased during the period 1998–2007. If sustained, this increase will have important implications for public health policy and planning.

Caroline J Lavender BA, BSc(Hons) · Lynne K Brown DipAppSci · Paul D R Johnson MB BS, PhD, FRACP

Objective: Design, setting and participants: Cross-sectional survey of Sydney residents during WHO Phase 5 of pandemic (H1N1) 2009. Members of the public were approached in shopping and pedestrian malls in seven areas of Sydney between 2 May and 29 May 2009 to undertake the survey. The survey was also made available by email.Main outcome measures: Perceived personal risk and seriousness of the disease, opinion on the government and health authorities’ response, feelings about quarantine and infection control methods, and potential compliance with antiviral prophylaxis.Results: Of 620 respondents, 596 (96%) were aware of pandemic (H1N1) 2009, but 44% (273/620) felt they did not have enough information about the situation. More than a third (38%; 235/620) ranked their risk of catching influenza during a pandemic as low. When asked how they felt pandemic influenza would affect their health if they were infected, only a third (33%; 206/620) said “very seriously”. Just over half of the respondents (58%; 360/620) believed the pandemic would be over within a year. Respondents rated quarantine and vaccination with a pandemic vaccine as more effective than hand hygiene for the prevention of pandemic influenza.Conclusions: Emphasising the efficacy of recommended actions (such as hand hygiene), risks from the disease and the possible duration of the outbreak may help to promote compliance with official advice.

Holly Seale BSc, PhD · Mary-Louise McLaws DipTropPH, MPH, PhD · Anita E Heywood BSc, MPH · Kirsten F Ward BHthSci(Public Health) · Chris P Lowbridge RN, BAppSci, MPH · Debbie Van · Jan Gralton BSc · C Raina MacIntyre MB BS, PhD, FRACP

To the Editor: Grayson and Johnson’s editorial of 17 June1 and Eizenberg’s viewpoint article of 1 July2 both betray blind spots regarding Victoria’s laboratory response to pandemic influenza (H1N1) 2009 (“swine flu”) and the role of the Victorian Infectious Diseases Reference Laboratory (VIDRL). Grayson and Johnson incorrectly suggest that Victoria’s swine flu infection case definition represented a barrier to laboratory testing and detection of disease spread. Between 18 April 2009 (when the second case was identified in the United States) and 18 May 2009 (when the first case was identified in Victoria), VIDRL tested more than 500 specimens for respiratory viruses. All 16 influenza viruses detected were seasonal influenza strains. Swine flu testing was appropriately reserved for cases with a high pre-test probability of being positive, and even in this at-risk population, no positive cases were detected. The same authors highlight VIDRL’s prominent role in public hospital testing for viral diseases, but mistakenly conflate this with public health laboratory support of infectious disease outbreaks, as if concentration of diagnostic virology at VIDRL were a matter of policy. VIDRL’s diagnostic service is available to Victorian health care institutions for as long as they elect to refer specimens. There is no barrier to decentralising this capacity through access to appropriate new technology and scientific expertise. Nevertheless, centralisation of laboratory capability with optimised specimen transport and reporting offers an arguably more efficient model, and is widely used for this reason. On the other hand, VIDRL’s public health role in supporting the Victorian Department of Human Services’ (DHS’s) outbreak response capability represents a deliberate centralisation of capacity — for good reasons. Public health laboratory testing needs enormous surge capacity — on 1 June 2009, for example, we processed 1004 specimens requiring 1401 swine flu polymerase chain reaction (PCR) tests in a laboratory normally doing 100 respiratory tests daily. Public health laboratories also require expertise to develop, validate and perform essential tests during the early high-pressure phase of an outbreak, while also working closely with the DHS to manage the large patient data flows that underpin public health actions. There is nothing visionary about frittering away this crucial response capacity by devolving responsibility to a series of small nodes, each below critical mass. Both Grayson and Johnson and Eizenberg make misleading generalisations about test turnaround times and refer to non-existent backlogs. On 1 June, the most demanding day of the swine flu outbreak, the mean turnaround time for the 1401 PCR tests performed was 24 hours, with 90% of samples being tested within 32 hours of receipt. There are several reasons outside VIDRL’s control why occasional delays might have occurred. Firstly, transport from point of collection to VIDRL was often slow (1–3 days, with few if any public hospitals achieving faster times). Secondly, more than 10% of samples arrived with missing or incorrect information regarding addresses for reports. Eizenberg should note the high number of general practitioners completing a private pathology provider’s request form but sending the specimen directly to VIDRL, causing delay while results went to the apparent referring laboratory. More than 200 specimens arrived with no request forms at all. Finally, many organisations had no mechanism in place for receipt of large numbers of test results late in the evening, when VIDRL was continuing to work. With Victoria’s move to the “Sustain” phase of the pandemic influenza plan on 3 June, test capacity was directed to defined clinically at-risk patients.3 Many hundreds of samples not meeting the criteria for testing continued to arrive each day. Between 5 and 16 June, these were stored but not tested, and an immediate report went to the sender saying so, and explaining why. Although the capacity to test approved samples was never under threat, stocks of key PCR reagents were transiently sufficiently limited in Australia to preclude testing of samples classified as not meriting a laboratory test in the first place. It may be this scenario that Eizenberg tries inaccurately to describe. It is disappointing to be drawn into exchanging correspondence in these pages rather than having a constructive debriefing together at the end of this outbreak. No criticism by us of laboratory colleagues is intended, as we know there is a shared sense of the logistic challenges with which we have grappled, and can improve together. However, the record still needs to be put straight for a small number of physicians with a more limited grasp of the issues.

Michael G Catton · Julian D Druce · Chris J Birch

To the Editor: The increasing overcrowding on public transport, particularly trains, in many Australian cities makes for considerable discomfort. As the problem deteriorates, concerns about attributable illness and even death have been raised.1 Overcrowding on public transport also contributes to the spread of respiratory diseases such as influenza (pandemic or otherwise).2 The risk of contracting influenza is greatest for people who are within 1 m of an infectious person, through exposure to respiratory droplets, particularly for periods of more than 15 minutes.3,4 Seasonal influenza, which infects millions of Australians annually — resulting in an estimated 2000 deaths and 10 000 hospitalisations5 — is a major health concern. As a resident of Melbourne and regular train commuter, personal observation supports recent claims of severe overcrowding,1 with the average number of people sitting or standing within 1 m of another person on Melbourne trains during peak periods having increased markedly over the past few years. If an average peak commuter is now placed within 1 m of 10 people for a prolonged period twice a day (a conservative estimate), at least 100 infectious influenza contacts potentially occur each week. With annual attack rates for seasonal influenza of 5%–10%,5 the likelihood of contracting infection while crammed into under-resourced train networks is significant. In the context of an influenza pandemic, with higher attack rates, the risk is even greater. Substantial community resources have appropriately been invested in pandemic planning and mitigation strategies. Perhaps we should devote some of these resources to public transport services to reduce overcrowding. Our national pandemic plan advises that A very simple way of reducing the chances of being infected or passing on infection is to stand or sit back from other people in public or in the workplace. Where possible, you should try to maintain a distance of at least a metre, which is about a large step.4 Such advice is impossible to follow on peak-period train services, certainly in Melbourne. Investment in train services to reduce the spread of infections would not only help delay the onset of the next influenza pandemic, but would also reduce seasonal influenza and other respiratory virus transmission. Furthermore, it could avert injuries and illness due to crushing and overheating/dehydration, and could conceivably reduce the road toll by taking cars off roads during peak hours. Few pandemic influenza planning investments could deliver such diverse public health dividends while we ride out the latest influenza pandemic and await the inevitable next one.

Benjamin C Cowie

To the Editor: A 79-year-old man from Gatton, 80 km west of Brisbane (Box 1), presented in July 2008 with an extensive area of cellulitis on the right knee surrounding a central ulcer 2 cm in diameter (Box 2). Gram staining of swabs taken from the ulcer showed polymorphs and gram-negative bacilli. An oxidase-positive, gentamicin-resistant, gram-negative bacillus was cultured. It had the biochemical profile and characteristic colonial morphology of Burkholderia pseudomallei, the causative organism of melioidosis. The identity of the organism was confirmed by polymerase chain reaction. Blood and urine cultures were negative, and a chest x-ray was normal. The patient was treated with intravenous ceftazidime 2 g four times a day for 10 days, as well as oral cotrimoxazole 320/1600 mg twice a day for 6 months. The infection appeared to be localised, and the patient made a successful recovery. Melioidosis can have a wide spectrum of clinical manifestations.1 Skin and soft tissue infections, as seen in our patient, may lead to fulminating systemic infections if treatment is inadequate.1 There were also several factors that predisposed our patient to melioidosis, including type 2 diabetes, renal impairment, and concurrent steroid treatment (for persistent sinusitis). The patient had a history of recent local exposure to floodwaters and soil: he had spent several hours kneeling in wet mud repairing a burst water pipe. Within a few days, an abrasion on the knee had developed into the presenting lesion. The patient denied visiting any areas where tropical melioidosis was endemic. In Australia, melioidosis is generally considered endemic in areas north of 20°S. In subtropical Australia, below 20°S, sporadic endemic infections in domestic animals and humans have occurred in south-eastern Queensland2-6 and south-western Western Australia.7 Three fatal human cases have been reported from the Brisbane River valley (two in 1996, near a reservoir 20 km north of Gatton;4 one in 1999, 5 km from Ipswich city centre5). All three patients were exposed to floodwaters, two had infected skin lesions, and all three progressed to fulminating pneumonia. All three also had alcohol-associated pathology, a recognised comorbidity.1 There were also two less well documented (but apparently local) human cases from the Brisbane region in 19676 and 1974.4 Recent molecular typing of five strains of B. pseudomallei isolated from south-eastern Queensland showed them to be genetically distinct from each other and from isolates obtained from tropical Australia, suggesting that this subtropical focus is most likely a natural phenomenon from ancient times.5 The reticulated water supply to our patient’s house was sourced from the Wivenhoe Dam. The source of the bacteria was most likely the local soil, which is of a heavy clay type suitable for this organism. The Brisbane River valley appears to be a subtropical endemic area for melioidosis, and further sporadic cases can be expected. 1 Location of melioidosis cases reported in Queensland 2 Area of cellulitis around a central ulcer on the patient’s right knee

Roger W Guard · Peter J Morero · Win Yi · Maureen J Mackay

To the Editor: Rickettsia australis is the causative organism of Queensland tick typhus, also known as Australian spotted fever. It is an obligate, intracellular organism that invades endothelial cells, causing vasculitis.1,2 Its transmission to humans is via Ixodes tick species, which can occur along the east coast of Australia, but predominantly occur in the north-east.3 R. australis was previously thought to have a low complication rate; however, severe sequelae such as multiorgan failure, severe pneumonia and digital necrosis have emerged in recent years.1 A 54-year-old woman with type 1 diabetes presented to a rural hospital in Queensland with a 1-week history of vomiting, diarrhoea, rigors, and fevers to 39.4°C. Her blood sugar level on arrival was 31 mmol/L (reference range [RR], 3.0–7.8 mmol/L) and diabetic ketoacidosis was diagnosed. Despite initial treatment, her condition continued to decline, and she was transferred to a tertiary referral centre. Her condition deteriorated into multiorgan failure, requiring ventilation and inotropic support. Triple antibiotic therapy comprising ciprofloxacin, meropenem and doxycycline was initiated. Results of blood cultures for anaerobic and aerobic bacteria and a vasculitic screen were negative. The patient underwent serial chest x-rays, which demonstrated a resolving left lower lobe collapse/consolidation and a right-sided pleural effusion. Paired sera from Day 1 and Day 11 of admission to the tertiary hospital were tested in parallel for antibodies to R. australis. A rise in R. australis antibody titre, from 256 to 1024 (RR, < 32), supported a diagnosis of rickettsial disease. Serum from Day 1 was negative for antibodies to Mycoplasma, Leptospira, and Brucella species. A family conference later suggested that the patient may have been bitten by an insect; however, no suspicious lesion was identified. Her treatment was changed to intravenous doxycycline monotherapy, and slow improvement was noted. Two days after admission, the patient developed widespread bullae and dermal necrosis with large areas of affected dermis sloughing off (Box), as well as digital and proximal foot ischaemia. A skin biopsy showed changes consistent with septic vasculitis. The patient was reviewed by a dermatologist, who concluded that it was unlikely to be from a drug reaction. Thirty-six days after admission, she underwent bilateral below-knee amputations. Formalisation of the stumps was delayed to ensure viable tissue for coverage. Necrotic areas of her lower limbs and arms were also debrided and grafted, and seven of her fingers were amputated at the level of the proximal interphalangeal joint. The patient was discharged to a smaller centre for ongoing rehabilitation and support. This case highlights the possible severity of R. australis infection, which can be complicated by septic shock, coagulopathy, multiorgan failure and digital gangrene. In addition, diabetes and the resultant ketoacidosis contributed to a compromised host and an unusually severe clinical course. Bullae and dermal necrosis on the legs of a patient with severe rickettsial disease

Theo F Birch · Michael Muller

West Nile virus is an arbovirus that has caused large outbreaks of febrile illness, meningitis and encephalitis in Europe, North America and the Middle East. We describe the first laboratory-confirmed human case of West Nile virus infection in Australia, in a 58-year-old tourist who was almost certainly infected in Israel. The case is a reminder of the need to consider exotic pathogens in travellers and of the risk of introducing new pathogens into Australia. Clinical recordA 58-year-old man presented to the emergency department of our hospital with chills, malaise, myalgia and epigastric pain. He was a tourist from Israel who had arrived in Australia with his family 3 days previously to visit relatives. The family flew directly from Tel Aviv to Melbourne, with a brief transit stop in Hong Kong airport. The patient reported a 5-day history of low-grade fevers, malaise, headache and epigastric discomfort, which started before he left Israel. He was previously well with no significant past medical history. He resided on a large cooperative farm in the southern district of Israel but worked in administration, with minimal contact with farm animals. He was not taking any regular medications, consumed alcohol infrequently and was a non-smoker. On examination, he had a temperature of 37.8°C and a diffuse erythematous macular rash. He was diagnosed with “viral illness”, treated symptomatically and discharged from the emergency department. On Day 7 of the illness, the patient re-presented to the emergency department increasingly unwell. Symptoms now included rigors, headache, dizziness and ear pain. On examination, he had a fever (temperature, 39.6°C), but no neck stiffness, photophobia or focal neurological deficit. After investigation and stabilisation in the emergency department, he was transferred to a ward for ongoing investigation by the infectious diseases team. Supportive care was instituted. Over the next 24 hours, the patient’s condition deteriorated with ongoing fevers and the onset of mild delirium and ataxia. A presumptive diagnosis of encephalitis was made, and diagnostic investigations were undertaken. Acyclovir was commenced empirically for herpes simplex encephalitis until this diagnosis was excluded. The patient’s fever began to resolve by Day 10 of the illness, and he was discharged after 18 days in hospital with mild ataxia. At outpatient review 2 weeks after discharge, he had persisting lethargy and mild ataxia. He returned to Israel with his family, where he underwent outpatient rehabilitation. InvestigationsExtensive investigations were undertaken to diagnose the aetiology of the encephalitis. Cerebrospinal fluid (CSF) sampled on Day 10 of the illness showed leukocytosis (polymorphs, 2 × 106/L; lymphocytes, 75 × 106/L; unidentified cells 12 × 106/L; and erythrocytes, 90 × 106/L), raised protein level (0.84 g/L; reference range [RR], 0.15–0.4 g/L), but a glucose level in the reference range (3.7 mmol/L; RR, 2.5–4.5 mmol/L). However, culture and polymerase chain reaction (PCR) tests for common viral and mycobacterial pathogens gave negative results. Serological testing of acute and convalescent blood samples for common viral and bacterial causes of encephalitis showed no acute infection. Appearance of the brain on magnetic resonance imaging (MRI) was unremarkable. Diagnosis of West Nile virusPaired sera from Day 9 and Day 31 of the illness were tested in parallel in a flavivirus group-reactive enzyme-linked immunosorbent assay (ELISA) for IgG and IgM. This showed a fourfold rise in IgG titre, and IgM seroconversion. The sera were then tested against a panel of flaviviruses for total antibody (by neutralisation) and for IgG and IgM (by immunofluorescence). The strongest reaction by immunofluorescence was against the New York 99 strain of West Nile virus (WNV; Box 1); seroconversion to this virus was confirmed by neutralisation (“gold standard”) tests (Box 2). A stored CSF sample tested positive for IgM against WNV by immunofluorescence. Flavivirus RNA was not detected in CSF or serum by PCR testing. DiscussionThis is the first report of a laboratory-confirmed human importation of WNV infection in Australia. The only previously diagnosed case of acute WNV infection in Australia was in a horse imported for the breeding season, which acquired the infection overseas but became symptomatic on arrival (unpublished data, Arbovirus Emerging Diseases Unit, CIDMLS, Westmead Hospital, Sydney, NSW). WNV transmission has not been recorded in Australia. WNV is a single-stranded RNA flavivirus that was first isolated in 1937 from a patient with fever in the West Nile District of Uganda.1 The virus exists in a bird–mosquito–bird cycle, with wild birds as the amplifying host and reservoir.2 It has been isolated from 43 species of mosquito, mostly bird-feeding members of the Culex genus. Humans and other mammals are incidental hosts, when bitten by infected mosquitoes. Since first described, WNV has spread widely, with an associated dramatic increase in disease severity.3,4 It is found in Africa, Europe and the Middle East, with large outbreaks identified during the past decade in Romania, North America and Israel.5-7 About 80% of patients with WNV infection are asymptomatic. The incubation period for symptomatic disease is 2–14 days. “West Nile fever” is a non-specific febrile illness that includes headache, myalgia, and occasional gastrointestinal symptoms and usually resolves spontaneously in less than a week.8 Acute neurological illness is uncommon, occurring in fewer than 1% of infections, and can present with meningitis, encephalitis or a poliomyelitis-like acute flaccid paralysis.9 Our patient was almost certainly infected in Israel, where WNV is endemic, with episodic outbreaks reported since the 1950s, most recently in 2000.7 Israel is the likely origin of the WNV strain now circulating widely in North America.6 In Australia, WNV is not routinely considered in locally acquired encephalitis but was investigated in our patient because of the country where he acquired the illness. Close communication was needed with the testing laboratory to convey a more detailed history and clinical description than is usual on a standard request form. The most frequent arboviral cause of encephalitis in Australia is Murray Valley encephalitis virus, which is endemic in northern Western Australia, the Northern Territory and northern Queensland, and has epidemic activity in southern Australia.10 Less common arboviral causes of locally acquired encephalitis include Japanese encephalitis virus and Kunjin virus.11 The latter shares 80% of its genome with WNV and has been classified as a subtype of WNV.12 It is endemic in northern tropical regions of Australia,13 and the usual presentation is as a febrile illness; it is a rare cause of encephalitis.11 There have been no reports of locally acquired flavivirus in Melbourne, Victoria, where our patient resided while in Australia. Infection with WNV was diagnosed retrospectively in our patient based on serological testing of acute and convalescent sera. WNV IgM concentration was then measured in a stored CSF sample. The initial low-positive serological results for flavivirus group IgG suggested the patient had previously been infected with another member of the flavivirus family. The fourfold rise in IgG titre and new detection of IgM antibodies to WNV indicated this presentation was a new infection. The strongest reaction was to the New York 99 strain of WNV, which is closely related to strains isolated in Israel. Reactions to the Sarafend strain of WNV and the closely related Kunjin virus were significantly weaker. Negative PCR results are common in WNV infection because of the low-level transient viraemia of WNV.8 Similarly, only about 30% of patients have abnormal MRI findings.8 Our patient’s presentation illustrates the common clinical features of encephalitis. Fever, headache, personality change or delirium and altered conscious state are typical, and focal neurological deficits and seizures may also occur.14 The onset can be gradual. In this case, encephalitis was diagnosed on Day 9 of the illness. Initially, headache and dizziness were attributed to systemic infection until further neurological symptoms became apparent. The CSF findings were also typical of encephalitis, with an elevated white cell count and protein concentration, and glucose concentration in the reference range.14 The likelihood of WNV causing encephalitis rather than an isolated febrile illness or meningitis increases with advanced age.9 From a public health perspective, this case raises the question of whether WNV could be introduced into Australia. Culex mosquitoes are distributed widely throughout the country, and recent research has confirmed that Australian Culex mosquitoes can be infected with, and transmit, the North American strain of WNV.15 However, because of the similarity between WNV and Kunjin virus, antibodies to the latter in vertebrate hosts may limit the infectivity and establishment of WNV in the Australian environment, depending on the geographic distribution of Kunjin virus.16 The type of animal harbouring, and thus importing, WNV is also important. Some research shows humans are likely to be “dead end hosts”, with a level of viraemia that is too low to transmit to an uninfected mosquito.17 This suggests the risk of secondary cases from our patient was very low. The inadvertent or illegal importation of infected mosquitoes or birds would pose a far greater risk of introducing WNV into Australia. This is the first human case of laboratory-confirmed WNV infection recorded in Australia. It highlights the importance of considering the geographic origin of illness in travellers and is a reminder of the various arboviral causes of encephalitis. It is also a reminder of the possibility of international travellers, human or otherwise, introducing new infective agents. Fortunately, spread of the virus beyond the index patient was unlikely in this case. We urge vigilance regarding the possible introduction of new pathogens to the Australian environment. Any concern should be reported promptly to the relevant state or territory authorities. 1 West Nile virus Transmission electron micrograph of the West Nile virus (from another case). (Original image, Cynthia Goldsmith, Centers for Disease Control and Prevention, Atlanta, Ga, USA.) 2 Antibody titres against a range of flaviviruses* in the patient’s acute (Day 9) and convalescent (Day 31) sera Antibody assay Day 9 Day 31 Enzyme-linked immunosorbent assay Flavivirus group IgG 100 400 IgM < 100 800 Immunofluorescence test West Nile virus (New York 99) IgG < 10 640 IgM < 10 40 West Nile virus (Sarafend) IgG < 10 20 IgM < 10 < 10 Kunjin virus IgG < 10 20 IgM < 10 < 10 Murray Valley encephalitis virus IgG < 10 < 10 IgM < 10 < 10 Neutralisation test West Nile virus (New York 99) < 10 2560 West Nile virus (Sarafend) < 10 40 Kunjin virus < 10 80 * Sera were tested against representatives of a range of West Nile virus groups: New York 99 (Lineage 1, Clade 1a); Kunjin (Lineage 1, Clade 1b), and Sarafend (Lineage 2).

Benjamin A Rogers MB BS · Linda Hueston MSc · Irani Ratnam MB BS, FRACP

To the Editor: We report a case of a 13-year-old girl with cystic fibrosis (CF) and chronic Pseudomonas aeruginosa lung infection who developed an unusual infection that was challenging to manage. At a regular review, and with no obvious change in clinical respiratory status, the patient’s forced expiratory volume in 1 second (FEV1) was 70% of the predicted value — a drop from her usual 90%. A subsequent 3-week admission, including treatment with standard antipseudomonal antibiotics, physiotherapy and addition of nebulised dornase alfa, did not significantly improve her lung function. She was discharged home on a trial of azithromycin. One month later, she had a non-productive cough, and a bronchoalveolar lavage specimen showed no growth on culture. Four months later, the patient presented with increased non-productive cough and sudden further deterioration in FEV1 to 52% of the predicted value. She was admitted and given standard intravenous antipseudomonal antibiotics. Culture of a repeat bronchoalveolar lavage specimen grew Mycobacterium abscessus, sensitive to clarithromycin, imipenem and amikacin; hence, the patient was given intravenous imipenem and amikacin for 3 weeks. During this period, high-resolution computed tomography (CT) of the patient’s chest showed mucus plugging, marked diffuse parenchymal involvement with typical “tree-in-bud” appearance and, surprisingly, given her poor lung function, only moderate bronchiectasis (Box). Two years earlier, results of a chest CT scan were normal. The patient was discharged home on long-term nebulised amikacin, oral ciprofloxacin and oral clarithromycin. Her lung function gradually improved after discharge and, 6 months later, her FEV1 was 69% of the predicted value and a sputum culture produced no growth. CF is a risk factor for non-tuberculous mycobacterial (NTM) lung disease, which is notoriously difficult to eradicate. A recent multicentre prospective study in the United States estimated that, in patients with CF who are older than 10 years, the prevalence of non-tuberculous mycobacterium was around 13%. The most common species were M. avium complex (72%) and M. abscessus (16%).1 Another study suggested that M. abscessus was more common in paediatric patients.2 Clinical signs and symptoms of NTM infections are usually difficult to distinguish from those of chronic respiratory infections that occur during the advanced stages of CF. High-resolution CT often reveals features of parenchymal involvement, as demonstrated in our patient. No guidelines exist for treating NTM infections in the CF population. However, for M. abscessus infection, oral clarithromycin in combination with intravenous amikacin and either cefoxitin or imipenem for 2–4 months has been recommended, with sputum surveillance for at least 12 months after a negative culture result.3 Suppressive maintenance therapy with clarithromycin, intermittent intravenous antibiotics and aerosolised amikacin have all been reported, but not confirmed by controlled studies. Surgical resection may be curative in localised disease. As the life expectancy of patients with CF improves, the prevalence of NTM infections is likely to increase. The American Thoracic Society recommends that all patients with CF who are on macrolide therapy should be screened annually for atypical mycobacteria.3 Atypical mycobacteria should always be borne in mind when treating patients with CF and an unexplained decline in lung function. Computed tomography scan showing diffuse parenchymal involvement, mucus plugging and moderate bronchiectasis in a girl with cystic fibrosis and non-tuberculous mycobacterial lung disease

Abdullah A Yousef · Adam Jaffé

To the Editor: Recycling water from sewage into drinking water was recently discussed in the Journal.1 Although this is technically feasible, we need to be very wary. Such recycling is associated with very high ongoing monetary and energy costs, but, most importantly from a health perspective, is a “very high-risk”2 proposal that reverses 150 years of good public health policy of striving to keep sewage out of our drinking water supplies. When we need to recycle water from highly contaminated sources, it is much safer to do so for industrial purposes using separated pipelines (as is done in Singapore and Brisbane). The most extensive scientific review on this issue concluded that putting it into drinking water should be a “last resort”, that should be adopted only if other measures — including other water sources, nonpotable reuse, and water conservation — have been evaluated and rejected as technically or economically infeasible.3 Sewage contains very high concentrations of pathogens and drugs. Viruses (the most difficult pathogens to remove) can occur in concentrations higher than 106 per litre — orders of magnitude higher than in even the most polluted rivers. The technical and human performance needed to remove viruses safely will have to be proportionately higher than current practice — difficult to achieve, as we already have skills shortages. We would also need to ensure that the system will work all the time. Reverse osmosis (RO) is the most effective way to remove viruses and drugs from sewage, and should remove virtually all viruses and drugs. Surprisingly, few in-use data are available to check this. RO membranes seem to leak. One study found that RO only removed 92% of antibiotics.4 Recent safety reviews, including an Australian review5 (based on the previous study3), showed viruses were still detected post-treatment at three of seven sites on some occasions. The calculated virus removal ranged from 87% to > 99.995%, which equates to a “log reduction” of 1 to 5. However, to produce safe drinking water from sewage, we need a consistent 9.5-log reduction for enteroviruses.2 Even Giardia was not always removed. This less than optimal performance was when the system was not known to be malfunctioning; lowered performance might occur as often as 5 days a year.6 Current surrogate testing (eg, organic carbon) can only detect a membrane leak (or bypass) of at least 1%, which is well short of meeting the 9.5-log reduction we need for virus removal and reasonable safety.2 We need real-time tests to show that there is adequate virus removal, rather than none at all or only becoming aware of a problem after processed but contaminated water is already in our reservoirs.

Peter J Collignon

In reply: We agree that augmentation of drinking water sources with recycled sewage goes against the traditional policy of separating the two, and that many factors including cost and energy use need consideration in securing future water supplies. Our editorial1 was not written to promote potable recycling, which ultimately is a political and societal decision, but rather to point out that the carefully considered Australian guidelines for water recycling2 have been developed to ensure that, if this form of recycling is contemplated, it is done in a manner that safeguards public health. Main messages in the recycling guidelines include the importance of risk assessment for each individual scheme; avoidance of complete reliance on any single technical step (including reverse osmosis) for removal of contaminants, via a “multiple barrier” approach; adequate operational and water quality verification monitoring; and optimising training and skills management within water treatment facilities. Importantly, credits given for “log removal” for each treatment step are based on verifiable on-line performance, not theoretical values.2 These practical messages are also fundamental to the way we manage our conventional drinking water supplies.3 Consequently, discussions about recycling help reinforce the importance of continual assessment of water management, regardless of the source, and help ensure we do not become complacent.

Karin S Leder · Joanne E O’Toole · Martha I Sinclair